Fluorescence imaging with fixed pattern noise cancellation

ABSTRACT

Fluorescence imaging with reduced fixed pattern noise is disclosed. A method includes actuating an emitter to emit a plurality of pulses of electromagnetic radiation and sensing reflected electromagnetic radiation resulting from the plurality of pulses of electromagnetic radiation with a pixel array of an image sensor. The method includes reducing fixed pattern noise in an exposure frame by subtracting a reference frame from the exposure frame. The method is such that at least a portion of the plurality of pulses of electromagnetic radiation emitted by the emitter comprises electromagnetic radiation having a wavelength from about 770 nm to about 790 nm.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/735,939, filed Jan. 7, 2020, and claims the benefit of U.S.Provisional Patent Application No. 62/864,218, filed Jun. 20, 2019,titled “HYPERSPECTRAL AND FLUORESCENCE IMAGING WITH FIXED PATTERN NOISECANCELLATION,” which is incorporated herein by reference in itsentirety, including but not limited to those portions that specificallyappear hereinafter, the incorporation by reference being made with thefollowing exception: In the event that any portion of theabove-referenced provisional application is inconsistent with thisapplication, this application supersedes the above-referencedprovisional application.

TECHNICAL FIELD

This disclosure is directed to digital imaging and is particularlydirected to fluorescence imaging in a light deficient environment.

BACKGROUND

Advances in technology have provided advances in imaging capabilitiesfor medical use. An endoscope may be used to look inside a body andexamine the interior of an organ or cavity of the body. Endoscopes areused for investigating a patient's symptoms, confirming a diagnosis, orproviding medical treatment. A medical endoscope may be used for viewinga variety of body systems and parts such as the gastrointestinal tract,the respiratory tract, the urinary tract, the abdominal cavity, and soforth. Endoscopes may further be used for surgical procedures such asplastic surgery procedures, procedures performed on joints or bones,procedures performed on the neurological system, procedures performedwithin the abdominal cavity, and so forth.

In some instances of endoscopic imaging, it may be beneficial ornecessary to view a space in color. A digital color image includes atleast three layers, or “color channels,” that cumulatively form an imagewith a range of hues. Each of the color channels measures the intensityand chrominance of light for a spectral band. Commonly, a digital colorimage includes a color channel for red, green, and blue spectral bandsof light (this may be referred to as a Red Green Blue or RGB image).Each of the red, green, and blue color channels include brightnessinformation for the red, green, or blue spectral band of light. Thebrightness information for the separate red, green, and blue layers arecombined to create the color image. Because a color image is made up ofseparate layers, a conventional digital camera image sensor includes acolor filter array that permits red, green, and blue visible lightwavelengths to hit selected pixel sensors. Each individual pixel sensorelement is made sensitive to red, green, or blue wavelengths and willonly return image data for that wavelength. The image data from thetotal array of pixel sensors is combined to generate the RGB image. Theat least three distinct types of pixel sensors consume significantphysical space such that the complete pixel array cannot fit in thesmall distal end of an endoscope.

Because a traditional image sensor cannot fit in the distal end of anendoscope, the image sensor is traditionally located in a handpiece unitof an endoscope that is held by an endoscope operator and is not placedwithin the body cavity. In such an endoscope, light is transmitted alongthe length of the endoscope from the handpiece unit to the distal end ofthe endoscope. This configuration has significant limitations.Endoscopes with this configuration are delicate and can be easilymisaligned or damaged when bumped or impacted during regular use. Thiscan significantly degrade the quality of the images and necessitate thatthe endoscope be frequently repaired or replaced.

The traditional endoscope with the image sensor placed in the handpieceunit is further limited to capturing only color images. However, in someimplementations, it may be desirable to capture images with fluorescenceimage data in addition to color image data. Fluorescence is the emissionof light by a substance that has absorbed light or other electromagneticradiation. Certain fluorescent materials “glow” or emit a distinct colorthat is visible to the human eye when the fluorescent material issubjected to ultraviolet light or other wavelengths of electromagneticradiation. Certain fluorescent materials will cease to glow nearlyimmediately when the radiation source stops.

Fluorescence occurs when an orbital electron of a molecule, atom, ornanostructure is excited by light or other electromagnetic radiation,and then relaxes to its ground state by emitting a photon from theexcited state. The specific frequencies of electromagnetic radiationthat excite the orbital electron, or are emitted by the photon duringrelaxation, are dependent on the atom, molecule, or nanostructure.Fluorescence imaging has numerous practical applications, includingmineralogy, gemology, medicine, spectroscopy for chemical sensors,detecting biological processes or signals, and others. Fluorescence canbe used in biochemistry and medicine as a non-destructive means fortracking or analyzing biological molecules. Some fluorescent reagents ordyes can be configured to attach to certain types of tissue and therebydraw attention to that type of tissue.

However, fluorescence imaging requires specialized emissions ofelectromagnetic radiation and specialized imaging sensors capable ofreading the specific relaxation wavelength for a specific fluorescentreagent. Different reagents or dyes are sensitive to differentwavelengths of electromagnetic radiation and emit different wavelengthsof electromagnetic radiation when fluoresced. A fluorescent imagingsystem may be highly specialized and tuned for a certain reagent or dye.Such imaging systems are useful for limited applications and are notcapable of fluorescing more than one reagent or structure during asingle imaging session. It is very costly to use multiple distinctimaging systems that are each configured for fluorescing a differentreagent. Additionally, it may be desirable to administer multiplefluorescent reagents in a single imaging session and view the multiplereagents in a single overlaid image.

In light of the foregoing, described herein are systems, methods, anddevices for fluorescent imaging in a light deficient environment. Suchsystems, methods, and devices may provide multiple datasets foridentifying critical structures in a body and providing precise andvaluable information about the body cavity.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting and non-exhaustive implementations of the disclosure aredescribed with reference to the following figures, wherein likereference numerals refer to like parts throughout the various viewsunless otherwise specified. Advantages of the disclosure will becomebetter understood with regard to the following description andaccompanying drawings where:

FIG. 1 is a schematic view of a system for digital imaging in a lightdeficient environment with a paired emitter and pixel array;

FIG. 2 is a system for providing illumination to a light deficientenvironment for endoscopic imaging;

FIG. 2A is a schematic diagram of complementary system hardware;

FIGS. 3A to 3D are illustrations of the operational cycles of a sensorused to construct an exposure frame;

FIG. 4A is a graphical representation of the operation of an embodimentof an electromagnetic emitter;

FIG. 4B is a graphical representation of varying the duration andmagnitude of the emitted electromagnetic pulse to provide exposurecontrol;

FIG. 5 is a graphical representation of an embodiment of the disclosurecombining the operational cycles of a sensor, the electromagneticemitter, and the emitted electromagnetic pulses of FIGS. 3A-4B, whichdemonstrate the imaging system during operation;

FIG. 6A is a schematic diagram of a process for recording a video withfull spectrum light over a period of time from t(0) to t(1);

FIG. 6B is a schematic diagram of a process for recording a video bypulsing portioned spectrum light over a period of time from t(0) tot(1);

FIGS. 7A-7E illustrate schematic views of the processes over an intervalof time for recording a frame of video for both full spectrum light andpartitioned spectrum light;

FIG. 8A illustrates a traditional image sensor with optical black pixelsdisposed around a recording area of active pixels;

FIG. 8B illustrates an embodiment of a minimal area image sensor;

FIG. 9 is a readout sequence of an embodiment of an image sensor;

FIG. 10 is a readout sequence of an embodiment of a minimal area imagesensor;

FIG. 11 is a graphical representation of a simple exponential smoothingpixel offset estimation with small and large values for w;

FIG. 12 is a graphical representation of a modulation of the simpleexponential smoothing index after a gain change;

FIG. 13 is a schematic diagram of a process flow for cancellation offixed pattern noise;

FIG. 14 is a schematic diagram of a process flow to be implemented by acontroller and/or monochrome image signal processor for generating avideo stream having RGB images with fluorescence data overlaid thereon;

FIG. 15 is a schematic diagram of method and hardware schematics for usewith a partitioned light system;

FIG. 16 is a schematic diagram of a process flow for performingcorrections and adjustments on digital image data;

FIG. 17 is a schematic diagram of a pattern reconstruction process forgenerating an RGB image with fluorescence data overlaid thereon bypulsing partitioned spectrums of light;

FIGS. 18A-18C illustrate a light source having a plurality of emitters;

FIG. 19 illustrates a single optical fiber outputting via a diffuser atan output to illuminate a scene in a light deficient environment;

FIG. 20 illustrates a portion of the electromagnetic spectrum dividedinto a plurality of different sub-spectrums which may be emitted byemitters of a light source in accordance with the principles andteachings of the disclosure;

FIG. 21 is a schematic diagram illustrating a timing sequence foremission and readout for generating an image frame comprising aplurality of exposure frames resulting from differing partitions ofpulsed light;

FIG. 22 illustrates an imaging system including a single cut filter forfiltering wavelengths of electromagnetic radiation;

FIG. 23 illustrates an imaging system comprising a multiple cut filterfor filtering wavelengths of electromagnetic radiation;

FIGS. 24A and 24B illustrate a perspective view and a side view,respectively, of an implementation of an imaging sensor having aplurality of pixel arrays for producing a three-dimensional image,wherein the plurality of pixel arrays and the image sensor are built ona plurality of substrates;

FIGS. 25A and 25B illustrate an implementation having a plurality ofpixel arrays for producing a three-dimensional image in accordance withthe principles and teachings of the disclosure; and

FIGS. 26A and 26B illustrate a perspective view and a side view,respectively, of an implementation of an imaging sensor built on aplurality of substrates, wherein a plurality of pixel columns formingthe pixel array are located on the first substrate and a plurality ofcircuit columns are located on a second substrate and showing anelectrical connection and communication between one column of pixels toits associated or corresponding column of circuitry.

DETAILED DESCRIPTION

Disclosed herein are systems, methods, and devices for digital imagingthat may be primarily suited to medical applications such as medicalendoscopic imaging. An embodiment of the disclosure is an endoscopicsystem for fluorescence and/or color imaging in a light deficientenvironment.

An embodiment of the disclosure is an endoscopic imaging system with aCMOS (Complementary Metal Oxide Semiconductor) image sensor. CMOS imagesensors suffer from multiple sources of image noise. Image noise israndom variation of brightness or color information and can be caused byelectronic noise. Image noise is generally undesirable and can degradethe quality of an image. Image noise can range from almost imperceptiblespecks on a digital image taken in good lighting conditions, to opticalimages that are almost entirely noise, from which only a small amount ofinformation can be derived by sophisticated image processing. The amountof noise in an image generated by a CMOS image sensor is dependent on awide range of physical conditions. Pure Poisson or Gaussian temporalnoise with no coherent components such as photon shot noise or sourcefollower read noise can look natural within a video stream. Other formsof perceivable noise will degrade image quality and may be unacceptablein some implementations.

One form of noise that can cause issues with CMOS image sensors isspatial noise (SN). Spatial noise has at least two sources, includingpixel fixed pattern noise (pixel FPN) and column fixed pattern noise(column FPN). Pixel fixed pattern noise is mostly due to variations inphotodiode leakage current (may be referred to as “dark signal”) frompixel to pixel. This source can be dependent on junction temperature andexposure time. Column fixed pattern noise is a consequence of thereadout architecture in which pixels from within the same column arechanneled through common analog readout elements. In manyimplementations, it is desirable to cancel out image noise andparticularly to cancel out fixed pattern noise. In light of theforegoing, disclosed herein are systems, methods, and devices forimaging in a light deficient environment and cancelling fixed patternnoise in resulting images.

Conventional endoscopes are designed such that the image sensor isplaced at a proximal end of the device within a handpiece unit. Thisconfiguration requires that incident light travel the length of theendoscope by way of precisely coupled optical elements. The preciseoptical elements can easily be misaligned during regular use, and thiscan lead to image distortion or image loss. Embodiments of thedisclosure place an image sensor within a distal end of the endoscopeitself. This provides greater optical simplicity when compared withimplementations known in the art. However, an acceptable solution tothis approach is by no means trivial and introduces its own set ofengineering challenges, not least of which that the image sensor mustfit within a highly constrained area. Disclosed herein are systems,methods, and devices for digital imaging in a light deficientenvironment that employ minimal area image sensors and can be configuredfor fluorescence and color imaging.

In some instances, it is desirable to generate endoscopic imaging withmultiple data types or multiple images overlaid on one another. Forexample, it may be desirable to generate an RGB image frame that furtherincludes fluorescence imaging data overlaid on the RGB image frame. Anoverlaid image of this nature may enable a medical practitioner orcomputer program to identify critical body structures based on thefluorescence imaging data. Historically, this would require the use ofmultiple sensor systems including an image sensor for color imaging andone or more additional image sensors for fluorescence imaging. In suchsystems, the multiple image sensors would have multiple types of pixelsensors that are each sensitive to distinct ranges of electromagneticradiation. In systems known in the art, this includes the three separatetypes of pixel sensors for generating an RGB color image along withadditional pixel sensors for generating the fluorescence image data atdifferent wavelengths of the electromagnetic spectrum. Traditionally,these multiple different pixel arrays consume a prohibitively largephysical space and cannot be located at a distal tip of the endoscope.Considering the foregoing, disclosed herein are systems, methods, anddevices for endoscopic imaging in a light deficient environment. Thesystems, methods, and devices disclosed herein provide means foremploying multiple imaging techniques in a single imaging session whilepermitting one or more image sensors to be disposed in a distal tip ofthe endoscope.

Fluorescence Imaging

The systems, methods, and devices disclosed herein provide means forgenerating fluorescence imaging data in a light deficient environment.The fluorescence imaging data may be used to identify certain materials,tissues, components, or processes within a body cavity or other lightdeficient environment. In certain embodiments, fluorescence imaging isprovided to a medical practitioner or computer-implemented program toenable the identification of certain structures or tissues within abody. Such fluorescence imaging data may be overlaid on black-and-whiteor RGB images to provide additional information and context.

Fluorescence is the emission of light by a substance that has absorbedlight or other electromagnetic radiation. Certain fluorescent materialsmay “glow” or emit a distinct color that is visible to the human eyewhen the fluorescent material is subjected to ultraviolet light or otherwavelengths of electromagnetic radiation. Certain fluorescent materialswill cease to glow nearly immediately when the radiation source stops.

Fluorescence occurs when an orbital electron of a molecule, atom, ornanostructure is excited by light or other electromagnetic radiation,and then relaxes to its ground state by emitting a photon from theexcited state. The specific frequencies of electromagnetic radiationthat excite the orbital electron, or are emitted by the photon duringrelaxation, are dependent on the particular atom, molecule, ornanostructure. In most cases, the light emitted by the substance has alonger wavelength, and therefore lower energy, than the radiation thatwas absorbed by the substance. However, when the absorbedelectromagnetic radiation is intense, it is possible for one electron toabsorb two photons. This two-photon absorption can lead to emission ofradiation having a shorter wavelength, and therefore higher energy, thanthe absorbed radiation. Additionally, the emitted radiation may also bethe same wavelength as the absorbed radiation.

Fluorescence imaging has numerous practical applications, includingmineralogy, gemology, medicine, spectroscopy for chemical sensors,detecting biological processes or signals, and so forth. Fluorescencemay particularly be used in biochemistry and medicine as anon-destructive means for tracking or analyzing biological molecules.The biological molecules, including certain tissues or structures, maybe tracked by analyzing the fluorescent emission of the biologicalmolecules after being excited by a certain wavelength of electromagneticradiation. However, relatively few cellular components are naturallyfluorescent. In certain implementations, it may be desirable tovisualize a certain tissue, structure, chemical process, or biologicalprocess that is not intrinsically fluorescent. In such animplementation, the body may be administered a dye or reagent that mayinclude a molecule, protein, or quantum dot having fluorescentproperties. The reagent or dye may then fluoresce after being excited bya certain wavelength of electromagnetic radiation. Different reagents ordyes may include different molecules, proteins, and/or quantum dots thatwill fluoresce at particular wavelengths of electromagnetic radiation.Thus, it may be necessary to excite the reagent or dye with aspecialized band of electromagnetic radiation to achieve fluorescenceand identify the desired tissue, structure, or process in the body.

Fluorescence imaging may provide valuable information in the medicalfield that may be used for diagnostic purposes and/or may be visualizedin real-time during a medical procedure. Specialized reagents or dyesmay be administered to a body to fluoresce certain tissues, structures,chemical processes, or biological processes. The fluorescence of thereagent or dye may highlight body structures such as blood vessels,nerves, particular organs, and so forth. Additionally, the fluorescenceof the reagent or dye may highlight conditions or diseases such ascancerous cells or cells experiencing a certain biological or chemicalprocess that may be associated with a condition or disease. Thefluorescence imaging may be used in real-time by a medical practitioneror computer program for differentiating between, for example, cancerousand non-cancerous cells during a surgical tumor extraction. Thefluorescence imaging may further be used as a non-destructive means fortracking and visualizing over time a condition in the body that wouldotherwise not be visible by the human eye or distinguishable in an RGBimage.

The systems, methods, and devices for generating fluorescence imagingdata may be used in coordination with reagents or dyes. Some reagents ordyes are known to attach to certain types of tissues and fluoresce atspecific wavelengths of the electromagnetic spectrum. In animplementation, a reagent or dye is administered to a patient that isconfigured to fluoresce when activated by certain wavelengths of light.The endoscopic imaging system disclosed herein is used to excite andfluoresce the reagent or dye. The fluorescence of the reagent or dye iscaptured by the endoscopic imaging system to aid in the identificationof tissues or structures in the body cavity. In an implementation, apatient is administered a plurality of reagents or dyes that are eachconfigured to fluoresce at different wavelengths and/or provide anindication of different structures, tissues, chemical reactions,biological processes, and so forth. In such an implementation, theendoscopic imaging system emits each of the applicable wavelengths tofluoresce each of the applicable reagents or dyes. This may negate theneed to perform individual imaging procedures for each of the pluralityof reagents or dyes.

Imaging reagents can enhance imaging capabilities in pharmaceutical,medical, biotechnology, diagnostic, and medical procedure industries.Many imaging techniques such as X-ray, computer tomography (CT),ultrasound, magnetic resonance imaging (MRI), and nuclear medicine,mainly analyze anatomy and morphology and are unable to detect changesat the molecular level. Fluorescent reagents, dyes, and probes,including quantum dot nanoparticles and fluorescent proteins, assistmedical imaging technologies by providing additional information aboutcertain tissues, structures, chemical processes, and/or biologicalprocesses that are present within the imaging region. Imaging usingfluorescent reagents enables cell tracking and/or the tracking ofcertain molecular biomarkers. Fluorescent reagents may be applied forimaging cancer, infection, inflammation, stem cell biology, and others.Numerous fluorescent reagents and dyes are being developed and appliedfor visualizing and tracking biological processes in a non-destructivemanner. Such fluorescent reagents may be excited by a certain wavelengthor band of wavelengths of electromagnetic radiation. Similarly, thosefluorescent reagents may emit relaxation energy at a certain wavelengthor band of wavelengths when fluorescing, and the emitted relaxationenergy may be read by a sensor to determine the location and/orboundaries of the reagent or dye.

In an embodiment of the disclosure, an endoscopic imaging system pulseselectromagnetic radiation for exciting an electron in a fluorescentreagent or dye. The endoscopic imaging system may pulse multipledifferent wavelengths of electromagnetic radiation for fluorescingmultiple different reagents or dyes during a single imaging session. Theendoscope includes an image sensor that is sensitive to the relaxationwavelength(s) of the one or more reagents or dyes. The imaging datagenerated by the image sensor can be used to identify a location andboundary of the one or more reagents or dyes. The endoscope system mayfurther pulse electromagnetic radiation in red, green, and blue bands ofvisible light such that the fluorescence imaging can be overlaid on anRGB video stream.

Pulsed Imaging

Some implementations of the disclosure include aspects of a combinedsensor and system design that allows for high definition imaging withreduced pixel counts in a controlled illumination environment. This isaccomplished with frame-by-frame pulsing of a single-color wavelengthand switching or alternating each frame between a single, differentcolor wavelength using a controlled light source in conjunction withhigh frame capture rates and a specially designed correspondingmonochromatic sensor. Additionally, electromagnetic radiation outsidethe visible light spectrum may be pulsed to enable the generation of afluorescence image. The pixels may be color agnostic such that eachpixel generates data for each pulse of electromagnetic radiation,including pulses for red, green, and blue visible light wavelengthsalong with other wavelengths used for fluorescence imaging.

For the purposes of promoting an understanding of the principles inaccordance with the disclosure, reference will now be made to theembodiments illustrated in the drawings and specific language will beused to describe the same. It will nevertheless be understood that nolimitation of the scope of the disclosure is thereby intended. Anyalterations and further modifications of the inventive featuresillustrated herein, and any additional applications of the principles ofthe disclosure as illustrated herein, which would normally occur to oneskilled in the relevant art and having possession of this disclosure,are to be considered within the scope of the disclosure claimed.

Before the structure, systems and methods for producing an image in alight deficient environment are disclosed and described, it is to beunderstood that this disclosure is not limited to the particularstructures, configurations, process steps, and materials disclosedherein as such structures, configurations, process steps, and materialsmay vary somewhat. It is also to be understood that the terminologyemployed herein is used for the purpose of describing particularembodiments only and is not intended to be limiting since the scope ofthe disclosure will be limited only by the appended claims andequivalents thereof.

In describing and claiming the subject matter of the disclosure, thefollowing terminology will be used in accordance with the definitionsset out below.

It must be noted that, as used in this specification and the appendedclaims, the singular forms “a,” “an,” and “the” include plural referentsunless the context clearly dictates otherwise.

As used herein, the terms “comprising,” “including,” “containing,”“characterized by,” and grammatical equivalents thereof are inclusive oropen-ended terms that do not exclude additional, unrecited elements ormethod steps.

As used herein, the phrase “consisting of” and grammatical equivalentsthereof exclude any element or step not specified in the claim.

As used herein, the phrase “consisting essentially of” and grammaticalequivalents thereof limit the scope of a claim to the specifiedmaterials or steps and those that do not materially affect the basic andnovel characteristic or characteristics of the claimed disclosure.

As used herein, the term “proximal” shall refer broadly to the conceptof a portion nearest an origin.

As used herein, the term “distal” shall generally refer to the oppositeof proximal, and thus to the concept of a portion farther from anorigin, or a furthest portion, depending upon the context.

As used herein, color sensors or multi spectrum sensors are thosesensors known to have a color filter array (CFA) thereon to filter theincoming electromagnetic radiation into its separate components. In thevisual range of the electromagnetic spectrum, such a CFA may be built ona Bayer pattern or modification thereon to separate green, red and bluespectrum components of the light.

As used herein, monochromatic sensor refers to an unfiltered imagingsensor. Since the pixels are color agnostic, the effective spatialresolution is appreciably higher than for their color (typicallyBayer-pattern filtered) counterparts in conventional single-sensorcameras. Monochromatic sensors may also have higher quantum efficiencybecause fewer incident photons are wasted between individual pixels.

As used herein, an emitter is a device that is capable of generating andemitting electromagnetic pulses. Various embodiments of emitters may beconfigured to emit pulses and have very specific frequencies or rangesof frequencies from within the entire electromagnetic spectrum. Pulsesmay comprise wavelengths from the visible and non-visible ranges. Anemitter may be cycled on and off to produce a pulse or may produce apulse with a shutter mechanism. An emitter may have variable poweroutput levels or may be controlled with a secondary device such as anaperture or filter. An emitter may emit broad spectrum or full spectrumelectromagnetic radiation that may produce pulses through colorfiltering or shuttering. An emitter may comprise a plurality ofelectromagnetic sources that act individually or in concert.

It should be noted that as used herein the term “light” is both aparticle and a wavelength and is intended to denote electromagneticradiation that is detectable by a pixel array 122 and may includewavelengths from the visible and non-visible spectrums ofelectromagnetic radiation. The term “partition” is used herein to mean apre-determined range of wavelengths of the electromagnetic spectrum thatis less than the entire spectrum, or in other words, wavelengths thatmake up some portion of the electromagnetic spectrum. As used herein, anemitter is a light source that may be controllable as to the portion ofthe electromagnetic spectrum that is emitted or that may operate as tothe physics of its components, the intensity of the emissions, or theduration of the emission, or all the above. An emitter may emit light inany dithered, diffused, or collimated emission and may be controlleddigitally or through analog methods or systems. As used herein, anelectromagnetic emitter is a source of a burst of electromagnetic energyand includes light sources, such as lasers, LEDs, incandescent light, orany light source that can be digitally controlled.

Referring now to the figures, FIG. 1 illustrates a schematic diagram ofa system 100 for sequential pulsed imaging in a light deficientenvironment. The system 100 can be deployed to generate an RGB imagewith fluorescence imaging data overlaid on the RGB image. The system 100includes an emitter 102 and a pixel array 122. The emitter 102 pulses apartition of electromagnetic radiation in the light deficientenvironment 112 and the pixel array 122 senses instances of reflectedelectromagnetic radiation. The emitter 102 and the pixel array 122 workin sequence such that one or more pulses of a partition ofelectromagnetic radiation results in image data sensed by the pixelarray 122.

It should be noted that as used herein the term “light” is both aparticle and a wavelength and is intended to denote electromagneticradiation that is detectable by a pixel array 122 and may includewavelengths from the visible and non-visible spectrums ofelectromagnetic radiation. The term “partition” is used herein to mean apre-determined range of wavelengths of the electromagnetic spectrum thatis less than the entire spectrum, or in other words, wavelengths thatmake up some portion of the electromagnetic spectrum. As used herein, anemitter is a light source that may be controllable as to the portion ofthe electromagnetic spectrum that is emitted or that may operate as tothe physics of its components, the intensity of the emissions, or theduration of the emission, or all the above. An emitter may emit light inany dithered, diffused, or collimated emission and may be controlleddigitally or through analog methods or systems. As used herein, anelectromagnetic emitter is a source of a burst of electromagnetic energyand includes light sources, such as lasers, LEDs, incandescent light, orany light source that can be digitally controlled.

A pixel array 122 of an image sensor may be paired with the emitter 102electronically, such that the emitter 102 and the pixel array 122 aresynced during operation for both receiving the emissions and for theadjustments made within the system. The emitter 102 may be tuned to emitelectromagnetic radiation in the form of a laser, which may be pulsed toilluminate a light deficient environment 112. The emitter 102 may pulseat an interval that corresponds to the operation and functionality ofthe pixel array 122. The emitter 102 may pulse light in a plurality ofelectromagnetic partitions such that the pixel array receiveselectromagnetic energy and produces a dataset that corresponds in timewith each specific electromagnetic partition. For example, FIG. 1illustrates an implementation wherein the emitter 102 emits fourdifferent partitions of electromagnetic radiation, including red 104,green 106, blue 108, and a fluorescence excitation 110 wavelength. Thefluorescence excitation 110 wavelength may include a plurality ofdifferent partitions of electromagnetic radiation that are selected tofluoresce a plurality of fluorescent reagents that are present withinthe light deficient environment 112. The fluorescent excitation 110wavelength may be selected to fluoresce a particular fluorescent reagentthat is present in the light deficient environment 112.

The light deficient environment 112 includes structures, tissues, andother elements that reflect a combination of red 114, green 116, and/orblue 118 light. A structure that is perceived as being red 114 willreflect back pulsed red 104 light. The reflection off the red structureresults in sensed red 105 by the pixel array 122 following the pulsedred 104 emission. The data sensed by the pixel array 122 results in ared exposure frame. A structure that is perceived as being green 116will reflect back pulsed green 106 light. The reflection off the greenstructure results in sensed green 107 by the pixel array 122 followingthe pulsed green 106 emission. The data sensed by the pixel array 122results in a green exposure frame. A structure that is perceived asbeing blue 118 will reflect back pulsed blue 108 light. The reflectionoff the blue structure results in sensed blue 109 by the pixel array 122following the pulsed blue 108 emission. The data sensed by the pixelarray 122 results in a blue exposure frame.

When a structure is a combination of colors, the structure will reflectback a combination of the pulsed red 104, pulsed green 106, and/orpulsed blue 108 emissions. For example, a structure that is perceived asbeing purple will reflect back light from the pulsed red 104 and pulsedblue 108 emissions. The resulting data sensed by the pixel array 122will indicate that light was reflected in the same region following thepulsed red 104 and pulsed blue 108 emissions. When the resultant redexposure frame and blue exposure frames are combined to form the RGBimage frame, the RGB image frame will indicate that the structure ispurple.

In an embodiment where the light deficient environment 112 includes afluorescent reagent or dye or includes one or more fluorescentstructures, tissues, or other elements, the pulsing scheme may includethe emission of a certain fluorescence excitation wavelength. Thecertain fluorescence excitation wavelength may be selected to fluorescea known fluorescent reagent, dye, or other structure. The fluorescentstructure will be sensitive to the fluorescence excitation wavelengthand will emit a fluorescence relaxation wavelength. The fluorescencerelaxation wavelength will be sensed by the pixel array 122 followingthe emission of the fluorescence excitation wavelength. The data sensedby the pixel array 122 results in a fluorescence exposure frame. Thefluorescence exposure frame may be combined with multiple other exposureframes to form an image frame. The data in the fluorescence exposureframe may be overlaid on an RGB image frame that includes data from ared exposure frame, a green exposure frame, and a blue exposure frame.

In an embodiment where the light deficient environment 112 includesstructures, tissues, or other materials that emit a spectral response tocertain partitions of the electromagnetic spectrum, the pulsing schememay include the emission of a hyperspectral partition of electromagneticradiation for the purpose of eliciting the spectral response from thestructures, tissues, or other materials present in the light deficientenvironment 112. The spectral response includes the emission orreflection of certain wavelengths of electromagnetic radiation. Thespectral response can be sensed by the pixel array 122 and result in ahyperspectral exposure frame. The hyperspectral exposure frame may becombined with multiple other exposure frames to form an image frame. Thedata in the hyperspectral exposure frame may be overlaid on an RGB imageframe that includes data from a red exposure frame, a green exposureframe, and a blue exposure frame.

In an embodiment, the pulsing scheme includes the emission of a lasermapping or tool tracking pattern. The reflected electromagneticradiation sensed by the pixel array 122 following the emission of thelaser mapping or tool tracking pattern results in a laser mappingexposure frame. The data in the laser mapping exposure frame may beprovided to a corresponding system to identify, for example, distancesbetween tools present in the light deficient environment 112, athree-dimensional surface topology of a scene in the light deficientenvironment 112, distances, dimensions, or positions of structures orobjects within the scene, and so forth. This data may be overlaid on anRGB image frame or otherwise provided to a user of the system.

The emitter 102 may be a laser emitter that is capable of emittingpulsed red 104 light for generating sensed red 105 data for identifyingred 114 elements within the light deficient environment 112. The emitter102 is further capable of emitting pulsed green 106 light for generatingsensed green 107 data for identifying green 116 elements within thelight deficient environment. The emitter 102 is further capable ofemitting pulsed blue 108 light for generating sensed blue 109 data foridentifying blue 118 elements within the light deficient environment.The emitter 102 is further capable of emitting pulsed fluorescenceexcitation 110 wavelength(s) of electromagnetic radiation foridentifying a fluorescent reagent 120 within the light deficientenvironment 112. The fluorescent reagent 120 is identified by excitingthe fluorescent reagent 120 with the pulsed fluorescence excitation 110light and then sensing (by the pixel array 122) the fluorescencerelaxation 111 wavelength for that particular fluorescent reagent 120.The emitter 102 is capable of emitting the pulsed red 104, pulsed green106, pulsed blue 108, and pulsed fluorescence excitation 110 wavelengthsin any desired sequence.

The pixel array 122 senses reflected electromagnetic radiation. Each ofthe sensed red 105, the sensed green 107, the sensed blue 109, and thesensed fluorescence relaxation 111 data can be referred to as an“exposure frame.” Each exposure frame is assigned a specific color orwavelength partition, wherein the assignment is based on the timing ofthe pulsed color or wavelength partition from the emitter 102. Theexposure frame in combination with the assigned specific color orwavelength partition may be referred to as a dataset. Even though thepixels 122 are not color-dedicated, they can be assigned a color for anygiven dataset based on a priori information about the emitter.

For example, during operation, after pulsed red 104 light is pulsed inthe light deficient environment 112, the pixel array 122 sensesreflected electromagnetic radiation. The reflected electromagneticradiation results in an exposure frame, and the exposure frame iscatalogued as sensed red 105 data because it corresponds in time withthe pulsed red 104 light. The exposure frame in combination with anindication that it corresponds in time with the pulsed red 104 light isthe “dataset.” This is repeated for each partition of electromagneticradiation emitted by the emitter 102. The data created by the pixelarray 122 includes the sensed red 105 exposure frame identifying red 114components in the light deficient environment and corresponding in timewith the pulsed red 104 light. The data further includes the sensedgreen 107 exposure frame identifying green 116 components in the lightdeficient environment and corresponding in time with the pulsed green106 light. The data further includes the sensed blue 109 exposure frameidentifying blue 118 components in the light deficient environment andcorresponding in time with the pulsed blue 108 light. The data furtherincludes the sensed fluorescence relaxation 111 exposure frameidentifying the fluorescent reagent 120 and corresponding in time withthe pulsed fluorescence excitation 110 wavelength(s) of light.

In one embodiment, three datasets representing RED, GREEN and BLUEelectromagnetic pulses are combined to form a single image frame. Thus,the information in a red exposure frame, a green exposure frame, and ablue exposure frame are combined to form a single RGB image frame. Oneor more additional datasets representing other wavelength partitions maybe overlaid on the single RGB image frame. The one or more additionaldatasets may represent, for example, fluorescence imaging responsive tothe pulsed excitation 110 wavelength between 770 nm and 790 nm andbetween 795 nm and 815 nm.

It will be appreciated that the disclosure is not limited to anyparticular color combination or any particular electromagneticpartition, and that any color combination or any electromagneticpartition may be used in place of RED, GREEN and BLUE, such as Cyan,Magenta and Yellow; Ultraviolet; infrared; any combination of theforegoing, or any other color combination, including all visible andnon-visible wavelengths, without departing from the scope of thedisclosure. In the figure, the light deficient environment 112 to beimaged includes red 114, green 116, and blue 118 portions, and furtherincludes a fluorescent reagent 120. As illustrated in the figure, thereflected light from the electromagnetic pulses only contains the datafor the portion of the object having the specific color that correspondsto the pulsed color partition. Those separate color (or color interval)datasets can then be used to reconstruct the image by combining thedatasets at 126. The information in each of the multiple exposure frames(i.e., the multiple datasets) may be combined by a controller 124, acontrol unit, a camera control unit, the image sensor, an image signalprocessing pipeline, or some other computing resource that isconfigurable to process the multiple exposure frames and combine thedatasets at 126. The datasets may be combined to generate the singleimage frame within the endoscope unit itself or offsite by some otherprocessing resource.

FIG. 2 is a system 200 for providing illumination to a light deficientenvironment, such as for endoscopic imaging. The system 200 may be usedin combination with any of the systems, methods, or devices disclosedherein. The system 200 includes an emitter 202, a controller 204, ajumper waveguide 206, a waveguide connector 208, a lumen waveguide 210,a lumen 212, and an image sensor 214 with accompanying opticalcomponents (such as a lens). The emitter 202 (may be genericallyreferred to as a “light source”) generates light that travels throughthe jumper waveguide 206 and the lumen waveguide 210 to illuminate ascene at a distal end of the lumen 212. The emitter 202 may be used toemit any wavelength of electromagnetic energy including visiblewavelengths, infrared, ultraviolet, hyperspectral, fluorescenceexcitation, laser scanning pulsing schemes, or other wavelengths. Thelumen 212 may be inserted into a patient's body for imaging, such asduring a procedure or examination. The light is output as illustrated bydashed lines 216. A scene illuminated by the light may be captured usingthe image sensor 214 and displayed for a doctor or some other medicalpersonnel. The controller 204 may provide control signals to the emitter202 to control when illumination is provided to a scene. In oneembodiment, the emitter 202 and controller 204 are located within acamera control unit (CCU) or external console to which an endoscope isconnected. If the image sensor 214 includes a CMOS sensor, light may beperiodically provided to the scene in a series of illumination pulsesbetween readout periods of the image sensor 214 during what is known asa blanking period. Thus, the light may be pulsed in a controlled mannerto avoid overlapping into readout periods of the image pixels in a pixelarray of the image sensor 214.

In one embodiment, the lumen waveguide 210 includes one or more opticalfibers. The optical fibers may be made of a low-cost material, such asplastic to allow for disposal of the lumen waveguide 210 and/or otherportions of an endoscope. In one embodiment, the lumen waveguide 210 isa single glass fiber having a diameter of 500 microns. The jumperwaveguide 206 may be permanently attached to the emitter 202. Forexample, a jumper waveguide 206 may receive light from an emitter withinthe emitter 202 and provide that light to the lumen waveguide 210 at thelocation of the connector 208. In one embodiment, the jumper waveguide106 includes one or more glass fibers. The jumper waveguide may includeany other type of waveguide for guiding light to the lumen waveguide210. The connector 208 may selectively couple the jumper waveguide 206to the lumen waveguide 210 and allow light within the jumper waveguide206 to pass to the lumen waveguide 210. In one embodiment, the lumenwaveguide 210 is directly coupled to a light source without anyintervening jumper waveguide 206.

The image sensor 214 includes a pixel array. In an embodiment, the imagesensor 214 includes two or more pixel arrays for generating athree-dimensional image. The image sensor 214 may constitute two moreimage sensors that each have an independent pixel array and can operateindependent of one another. The pixel array of the image sensor 214includes active pixels and optical black (“OB”) or optically blindpixels. The active pixels may be clear “color agnostic” pixels that arecapable of sensing imaging data for any wavelength of electromagneticradiation. The optical black pixels are read during a blanking period ofthe pixel array when the pixel array is “reset” or calibrated. In anembodiment, light is pulsed during the blanking period of the pixelarray when the optical black pixels are being read. After the opticalblack pixels have been read, the active pixels are read during a readoutperiod of the pixel array. The active pixels may be charged by theelectromagnetic radiation that is pulsed during the blanking period suchthat the active pixels are ready to be read by the image sensor duringthe readout period of the pixel array.

FIG. 2A is a schematic diagram of complementary system hardware such asa special purpose or general-purpose computer. Implementations withinthe scope of the present disclosure may also include physical and othernon-transitory computer readable media for carrying or storing computerexecutable instructions and/or data structures. Such computer readablemedia can be any available media that can be accessed by a generalpurpose or special purpose computer system. Computer readable media thatstores computer executable instructions are computer storage media(devices). Computer readable media that carry computer executableinstructions are transmission media. Thus, by way of example, and notlimitation, implementations of the disclosure can comprise at least twodistinctly different kinds of computer readable media: computer storagemedia (devices) and transmission media.

Computer storage media (devices) includes RAM, ROM, EEPROM, CD-ROM,solid state drives (“SSDs”) (e.g., based on RAM), Flash memory,phase-change memory (“PCM”), other types of memory, other optical diskstorage, magnetic disk storage or other magnetic storage devices, or anyother medium which can be used to store desired program code means inthe form of computer executable instructions or data structures andwhich can be accessed by a general purpose or special purpose computer.

A “network” is defined as one or more data links that enable thetransport of electronic data between computer systems and/or modulesand/or other electronic devices. In an implementation, a sensor andcamera control unit may be networked to communicate with each other, andother components, connected over the network to which they areconnected. When information is transferred or provided over a network oranother communications connection (either hardwired, wireless, or acombination of hardwired or wireless) to a computer, the computerproperly views the connection as a transmission medium. Transmissionsmedia can include a network and/or data links, which can be used tocarry desired program code means in the form of computer executableinstructions or data structures and which can be accessed by a generalpurpose or special purpose computer. Combinations of the above shouldalso be included within the scope of computer readable media.

Further, upon reaching various computer system components, program codemeans in the form of computer executable instructions or data structuresthat can be transferred automatically from transmission media tocomputer storage media (devices) (or vice versa). For example, computerexecutable instructions or data structures received over a network ordata link can be buffered in RAM within a network interface module(e.g., a “NIC”), and then eventually transferred to computer system RAMand/or to less volatile computer storage media (devices) at a computersystem. RAM can also include solid state drives (SSDs or PCIx based realtime memory tiered storage, such as FusionIO). Thus, it should beunderstood that computer storage media (devices) can be included incomputer system components that also (or even primarily) utilizetransmission media.

Computer executable instructions comprise, for example, instructions anddata which, when executed by one or more processors, cause ageneral-purpose computer, special purpose computer, or special purposeprocessing device to perform a certain function or group of functions.The computer executable instructions may be, for example, binaries,intermediate format instructions such as assembly language, or evensource code. Although the subject matter has been described in languagespecific to structural features and/or methodological acts, it is to beunderstood that the subject matter defined in the appended claims is notnecessarily limited to the described features or acts described above.Rather, the described features and acts are disclosed as example formsof implementing the claims.

Those skilled in the art will appreciate that the disclosure may bepracticed in network computing environments with many types of computersystem configurations, including, personal computers, desktop computers,laptop computers, message processors, control units, camera controlunits, hand-held devices, hand pieces, multi-processor systems,microprocessor-based or programmable consumer electronics, network PCs,minicomputers, mainframe computers, mobile telephones, PDAs, tablets,pagers, routers, switches, various storage devices, and the like. Itshould be noted that any of the above-mentioned computing devices may beprovided by or located within a brick and mortar location. Thedisclosure may also be practiced in distributed system environmentswhere local and remote computer systems, which are linked (either byhardwired data links, wireless data links, or by a combination ofhardwired and wireless data links) through a network, both performtasks. In a distributed system environment, program modules may belocated in both local and remote memory storage devices.

Further, where appropriate, functions described herein can be performedin one or more of: hardware, software, firmware, digital components, oranalog components. For example, one or more application specificintegrated circuits (ASICs) or field programmable gate arrays (FPGAs)can be programmed to carry out one or more of the systems and proceduresdescribed herein. Certain terms are used throughout the followingdescription and Claims to refer to particular system components. As oneskilled in the art will appreciate, components may be referred to bydifferent names. This document does not intend to distinguish betweencomponents that differ in name, but not function.

FIG. 2A is a block diagram illustrating an example computing device 250.Computing device 250 may be used to perform various procedures, such asthose discussed herein. Computing device 250 can function as a server, aclient, or any other computing entity. Computing device 250 can performvarious monitoring functions as discussed herein, and can execute one ormore application programs, such as the application programs describedherein. Computing device 250 can be any of a wide variety of computingdevices, such as a desktop computer, a notebook computer, a servercomputer, a handheld computer, camera control unit, tablet computer andthe like.

Computing device 250 includes one or more processor(s) 252, one or morememory device(s) 254, one or more interface(s) 256, one or more massstorage device(s) 258, one or more Input/Output (I/O) device(s) 260, anda display device 280 all of which are coupled to a bus 262. Processor(s)252 include one or more processors or controllers that executeinstructions stored in memory device(s) 254 and/or mass storagedevice(s) 258. Processor(s) 252 may also include various types ofcomputer readable media, such as cache memory.

Memory device(s) 254 include various computer readable media, such asvolatile memory (e.g., random access memory (RAM) 264) and/ornonvolatile memory (e.g., read-only memory (ROM) 266). Memory device(s)254 may also include rewritable ROM, such as Flash memory.

Mass storage device(s) 258 include various computer readable media, suchas magnetic tapes, magnetic disks, optical disks, solid-state memory(e.g., Flash memory), and so forth. As shown in FIG. 2 , a particularmass storage device is a hard disk drive 274. Various drives may also beincluded in mass storage device(s) 258 to enable reading from and/orwriting to the various computer readable media. Mass storage device(s)258 include removable media 276 and/or non-removable media.

I/O device(s) 260 include various devices that allow data and/or otherinformation to be input to or retrieved from computing device 250.Example I/O device(s) 260 include digital imaging devices,electromagnetic sensors and emitters, cursor control devices, keyboards,keypads, microphones, monitors or other display devices, speakers,printers, network interface cards, modems, lenses, CCDs or other imagecapture devices, and the like.

Display device 280 includes any type of device capable of displayinginformation to one or more users of computing device 250. Examples ofdisplay device 280 include a monitor, display terminal, video projectiondevice, and the like.

Interface(s) 256 include various interfaces that allow computing device250 to interact with other systems, devices, or computing environments.Example interface(s) 256 may include any number of different networkinterfaces 270, such as interfaces to local area networks (LANs), widearea networks (WANs), wireless networks, and the Internet. Otherinterface(s) include user interface 268 and peripheral device interface272. The interface(s) 256 may also include one or more user interfaceelements 268. The interface(s) 256 may also include one or moreperipheral interfaces such as interfaces for printers, pointing devices(mice, track pad, etc.), keyboards, and the like.

Bus 262 allows processor(s) 252, memory device(s) 254, interface(s) 256,mass storage device(s) 258, and I/O device(s) 260 to communicate withone another, as well as other devices or components coupled to bus 262.Bus 262 represents one or more of several types of bus structures, suchas a system bus, PCI bus, IEEE 1394 bus, USB bus, and so forth.

For purposes of illustration, programs and other executable programcomponents are shown herein as discrete blocks, although it isunderstood that such programs and components may reside at various timesin different storage components of computing device 250 and are executedby processor(s) 252. Alternatively, the systems and procedures describedherein can be implemented in hardware, or a combination of hardware,software, and/or firmware. For example, one or more application specificintegrated circuits (ASICs) or field programmable gate arrays (FPGAs)can be programmed to carry out one or more of the systems and proceduresdescribed herein.

FIG. 3A illustrates the operational cycles of a sensor used in rollingreadout mode or during the sensor readout 300. The frame readout periodmay start at and may be represented by vertical line 310. The readoutperiod 302 is represented by the diagonal or slanted line. The sensormay be read out on a row by row basis, the top of the downwards slantededge being the sensor top row 312 and the bottom of the downwardsslanted edge being the sensor bottom row 314. The time between the lastrow readout and the next readout period may be called the blankingperiod 316. It should be noted that some of the sensor pixel rows mightbe covered with a light shield (e.g., a metal coating or any othersubstantially black layer of another material type). These covered pixelrows may be referred to as optical black rows 318 and 320. Optical blackrows 318 and 320 may be used as input for correction algorithms. Asshown in FIG. 3A, these optical black rows 318 and 320 may be located onthe top of the pixel array or at the bottom of the pixel array or at thetop and the bottom of the pixel array.

FIG. 3B illustrates a process of controlling the amount ofelectromagnetic radiation, e.g., light, that is exposed to a pixel,thereby integrated or accumulated by the pixel. It will be appreciatedthat photons are elementary particles of electromagnetic radiation.Photons are integrated, absorbed, or accumulated by each pixel andconverted into an electrical charge or current. An electronic shutter orrolling shutter (shown by dashed line 322) may be used to start theintegration time by resetting the pixel. The light will then integrateuntil the next readout period. The position of the electronic shutter322 can be moved between two readout periods 302 to control the pixelsaturation for a given amount of light. It should be noted that thistechnique allows for a constant integration time between two differentlines but introduces a delay when moving from top to bottom rows.

FIG. 3C illustrates the case where the electronic shutter 322 has beenremoved. In this configuration, the integration of the incoming lightmay start during the readout period 302 and may end at the next readoutperiod 302, which also defines the start of the next integration.

FIG. 3D shows a configuration without an electronic shutter 322, butwith a controlled and pulsed light 330 during the blanking period 316.This ensures that all rows see the same light issued from the same lightpulse 330. In other words, each row will start its integration in a darkenvironment, which may be at the optical black back row 320 of read outframe (m) for a maximum light pulse width, and will then receive a lightstrobe and will end its integration in a dark environment, which may beat the optical black front row 318 of the next succeeding read out frame(m+1) for a maximum light pulse width. In the FIG. 3D example, the imagegenerated from the light pulse will be solely available during frame(m+1) readout without any interference with frames (m) and (m+2). Itshould be noted that the condition to have a light pulse to be read outonly in one frame and not interfere with neighboring frames is to havethe given light pulse firing during the blanking period 316. Because theoptical black rows 318, 320 are insensitive to light, the optical blackback rows 320 time of frame (m) and the optical black front rows 318time of frame (m+1) can be added to the blanking period 316 to determinethe maximum range of the firing time of the light pulse 330.

As illustrated in the FIG. 3A, a sensor may be cycled many times toreceive data for each pulsed color or wavelength (e.g., Red, Green,Blue, or other wavelength on the electromagnetic spectrum). Each cyclemay be timed. In an embodiment, the cycles may be timed to operatewithin an interval of 16.67 ms. In another embodiment, the cycles may betimed to operate within an interval of 8.3 ms. It will be appreciatedthat other timing intervals are contemplated by the disclosure and areintended to fall within the scope of this disclosure.

FIG. 4A graphically illustrates the operation of an embodiment of anelectromagnetic emitter. An emitter may be timed to correspond with thecycles of a sensor, such that electromagnetic radiation is emittedwithin the sensor operation cycle and/or during a portion of the sensoroperation cycle. FIG. 4A illustrates Pulse 1 at 402, Pulse 2 at 404, andPulse 3 at 406. In an embodiment, the emitter may pulse during thereadout period 302 of the sensor operation cycle. In an embodiment, theemitter may pulse during the blanking period 316 of the sensor operationcycle. In an embodiment, the emitter may pulse for a duration that isduring portions of two or more sensor operational cycles. In anembodiment, the emitter may begin a pulse during the blanking period316, or during the optical black portion 320 of the readout period 302,and end the pulse during the readout period 302, or during the opticalblack portion 318 of the readout period 302 of the next succeedingcycle. It will be understood that any combination of the above isintended to fall within the scope of this disclosure as long as thepulse of the emitter and the cycle of the sensor correspond.

FIG. 4B graphically represents varying the duration and magnitude of theemitted electromagnetic pulse (e.g., Pulse 1 at 412, Pulse 2 at 414, andPulse 3 at 416) to control exposure. An emitter having a fixed outputmagnitude may be pulsed during any of the cycles noted above in relationto FIGS. 3D and 4A for an interval to provide the needed electromagneticenergy to the pixel array. An emitter having a fixed output magnitudemay be pulsed at a longer interval of time, thereby providing moreelectromagnetic energy to the pixels or the emitter may be pulsed at ashorter interval of time, thereby providing less electromagnetic energy.Whether a longer or shorter interval time is needed depends upon theoperational conditions.

In contrast to adjusting the interval of time the emitter pulses a fixedoutput magnitude, the magnitude of the emission itself may be increasedto provide more electromagnetic energy to the pixels. Similarly,decreasing the magnitude of the pulse provides less electromagneticenergy to the pixels. It should be noted that an embodiment of thesystem may have the ability to adjust both magnitude and durationconcurrently, if desired. Additionally, the sensor may be adjusted toincrease its sensitivity and duration as desired for optimal imagequality. FIG. 4B illustrates varying the magnitude and duration of thepulses. In the illustration, Pulse 1 at 412 has a higher magnitude orintensity than either Pulse 2 at 414 or Pulse 3 at 416. Additionally,Pulse 1 at 412 has a shorter duration than Pulse 2 at 414 or Pulse 3 at416, such that the electromagnetic energy provided by the pulse isillustrated by the area under the pulse shown in the illustration. Inthe illustration, Pulse 2 at 414 has a relatively low magnitude orintensity and a longer duration when compared to either Pulse 1 at 412or Pulse 3 at 416. Finally, in the illustration, Pulse 3 at 416 has anintermediate magnitude or intensity and duration, when compared to Pulse1 at 412 and Pulse 2 at 414.

FIG. 5 is a graphical representation of an embodiment of the disclosurecombining the operational cycles, the electromagnetic emitter, and theemitted electromagnetic pulses of FIGS. 3A-3D and 4A to demonstrate theimaging system during operation in accordance with the principles andteachings of the disclosure. As can be seen in the figure, theelectromagnetic emitter pulses the emissions primarily during theblanking period 316 of the image sensor such that the pixels will becharged and ready to read during the readout period 302 of the imagesensor cycle. The dashed lines in FIG. 5 represent the pulses ofelectromagnetic radiation (from FIG. 4A). The pulses of electromagneticradiation are primarily emitted during the blanking period 316 of theimage sensor but may overlap with the readout period 302 of the imagesensor.

An exposure frame includes the data read by the pixel array of the imagesensor during a readout period 302. The exposure frame may be combinedwith an indication of what type of pulse was emitted by the emitterprior to the readout period 302. The combination of the exposure frameand the indication of the pulse type may be referred to as a dataset.Multiple exposure frames may be combined to generate a black-and-whiteor RGB color image. Additionally, hyperspectral, fluorescence, and/orlaser mapping imaging data may be overlaid on a black-and-white or RGBimage.

In an embodiment, an exposure frame is the data sensed by the pixelarray during the readout period 302 that occurs subsequent to a blankingperiod 316. The emission of electromagnetic radiation is emitted duringthe blanking period 316. In an embodiment, a portion of the emission ofelectromagnetic radiation overlaps the readout period 302. The blankingperiod 316 occurs when optical black pixels of the pixel array are beingread and the readout period 302 occurs when active pixels of the pixelarray are being read. The blanking period 316 may overlap the readoutperiod 302.

FIGS. 6A and 6B illustrate processes for recording an image frame.Multiple image frames may be strung together to generate a video stream.A single image frame may include data from multiple exposure frames,wherein an exposure frame is the data sensed by a pixel array subsequentto an emission of electromagnetic radiation. FIG. 6A illustrates atraditional process that is typically implemented with a color imagesensor having a color filter array (CFA) for filtering out certainwavelengths of light per pixel. FIG. 6B is a process that is disclosedherein and can be implemented with a monochromatic “color agnostic”image sensor that is receptive to all wavelengths of electromagneticradiation.

The process illustrated in FIG. 6A occurs from time t(0) to time t(1).The process begins with a white light emission 602 and sensing whitelight 604. The image is processed and displayed at 606 based on thesensing at 604.

The process illustrated in FIG. 6B occurs from time t(0) to time t(1).The process begins with an emission of green light 612 and sensingreflected electromagnetic radiation 614 subsequent to the emission ofgreen light 612. The process continues with an emission of red light 616and sensing reflected electromagnetic radiation 618 subsequent to theemission of red light 616. The process continues with an emission ofblue light 620 and sensing reflected electromagnetic radiation 622subsequent to the emission of blue light 620. The process continues withone or more emissions of a fluorescence excitation wavelengths 624 andsensing reflected electromagnetic energy 626 subsequent to each of theone or more emissions of fluorescence excitation wavelengths ofelectromagnetic radiation 624. The image is processed and displayed at628 based on each of the sensed reflected electromagnetic energyinstances 614, 618, 622, and 626.

The process illustrated in FIG. 6B provides a higher resolution imageand provides a means for generating an RGB image that further includesfluorescence imaging data. When partitioned spectrums of light are used,(as in FIG. 6B) a sensor can be made sensitive to all wavelengths ofelectromagnetic energy. In the process illustrated in FIG. 6B, themonochromatic pixel array is instructed that it is sensingelectromagnetic energy from a predetermined partition of the fullspectrum of electromagnetic energy in each cycle. Therefore, to form animage the sensor need only be cycled with a plurality of differingpartitions from within the full spectrum of light. The final image isassembled based on the multiple cycles. Because the image from eachcolor partition frame cycle has a higher resolution (compared with a CFApixel array), the resultant image created when the partitioned lightframes are combined also has a higher resolution. In other words,because each and every pixel within the array (instead of, at most,every second pixel in a sensor with a CFA) is sensing the magnitudes ofenergy for a given pulse and a given scene, just fractions of timeapart, a higher resolution image is created for each scene.

As can be seen graphically in the embodiments illustrated in FIGS. 6Aand 6B between times t(0) and t(1), the sensor for the partitionedspectrum system in FIG. 6B has cycled at least four times for every oneof the full spectrum system in FIG. 6A. In an embodiment, a displaydevice (LCD panel) operates at 50-60 frames per second. In such anembodiment, the partitioned light system in FIG. 6B may operate at200-240 frames per second to maintain the continuity and smoothness ofthe displayed video. In other embodiments, there may be differentcapture and display frame rates. Furthermore, the average capture ratecould be any multiple of the display rate.

In an embodiment, it may be desired that not all partitions berepresented equally within the system frame rate. In other words, notall light sources have to be pulsed with the same regularity so as toemphasize and de-emphasize aspects of the recorded scene as desired bythe users. It should also be understood that non-visible and visiblepartitions of the electromagnetic spectrum may be pulsed together withina system with their respective data value being stitched into the videooutput as desired for display to a user.

An embodiment may comprise a pulse cycle pattern as follows:

-   -   i. Green pulse;    -   ii. Red pulse;    -   iii. Blue pulse;    -   iv. Green pulse;    -   v. Red pulse;    -   vi. Blue pulse;    -   vii. Fluorescence excitation pulse;    -   viii. (Repeat)

As can be seen in the example, a fluorescence excitation partition maybe pulsed at a rate differing from the rates of the other partitionpulses. This may be done to emphasize a certain aspect of the scene,with the fluorescence imaging data simply being overlaid with the otherdata in the video output to make the desired emphasis. It should benoted that the addition of a fluorescence partition on top of the RED,GREEN, and BLUE partitions does not necessarily require the serializedsystem to operate at four times the rate of a full spectrum non-serialsystem because every partition does not have to be represented equallyin the pulse pattern. As seen in the embodiment, the addition of apartition pulse that is represented less in a pulse pattern(fluorescence excitation in the above example), would result in anincrease of less than 20% of the cycling speed of the sensor toaccommodate the irregular partition sampling.

In various embodiments, the pulse cycle pattern may further include anyof the following wavelengths in any suitable order. Such wavelengths maybe particularly suited for exciting a fluorescent reagent to generatefluorescence imaging data by sensing the relaxation emission of thefluorescent reagent based on a fluorescent reagent relaxation emission:

-   -   i. 770±20 nm;    -   ii. 770±10 nm;    -   iii. 770±5 nm;    -   iv. 790±20 nm;    -   v. 790±10 nm;    -   vi. 790±5 nm;    -   vii. 795±20 nm;    -   viii. 795±10 nm;    -   ix. 795±5 nm;    -   x. 815±20 nm;    -   xi. 815±10 nm;    -   xii. 815±5 nm;    -   xiii. 770 nm to 790 nm; and/or    -   xiv. 795 nm to 815 nm.

The partition cycles may be divided so as to accommodate or approximatevarious imaging and video standards. In an embodiment, the partitioncycles may comprise pulses of electromagnetic energy in the Red, Green,and Blue spectrum as follows as illustrated best in FIGS. 7A-7D. In FIG.7A, the different light intensities have been achieved by modulating thelight pulse width or duration within the working range shown by thevertical grey dashed lines. In FIG. 7B, the different light intensitieshave been achieved by modulating the light power or the power of theelectromagnetic emitter, which may be a laser or LED emitter, butkeeping the pulse width or duration constant. FIG. 7C shows the casewhere both the light power and the light pulse width are beingmodulated, leading to greater flexibility. The partition cycles may useCyan Magenta Yellow (CMY), infrared, ultraviolet, hyperspectral, andfluorescence using a non-visible pulse source mixed with visible pulsesources and any other color space required to produce an image orapproximate a desired video standard that is currently known or yet tobe developed. It should also be understood that a system may be able toswitch between the color spaces on the fly to provide the desired imageoutput quality.

In an embodiment using color spaces Green-Blue-Green-Red (as seen inFIG. 7D) it may be desirous to pulse the luminance components more oftenthan the chrominance components because users are generally moresensitive to light magnitude differences than to light colordifferences. This principle can be exploited using a mono-chromaticsensor as illustrated in FIG. 7D. In FIG. 7D, green, which contains themost luminance information, may be pulsed more often or with moreintensity in a (G B G R G B G R . . . ) scheme to obtain the luminancedata. Such a configuration would create a video stream that hasperceptively more detail, without creating and transmittingunperceivable data.

In an embodiment, duplicating the pulse of a weaker partition may beused to produce an output that has been adjusted for the weaker pulse.For example, blue laser light is considered weak relative to thesensitivity of silicon-based pixels and is difficult to produce incomparison to the red or green light, and therefore may be pulsed moreoften during a frame cycle to compensate for the weakness of the light.These additional pulses may be done serially over time or by usingmultiple lasers that simultaneously pulse to produce the desiredcompensation effect. It should be noted that by pulsing during ablanking period (time during which the sensor is not reading out thepixel array), the sensor is insensitive to differences/mismatchesbetween lasers of the same kind and simply accumulates the light for thedesired output. In another embodiment, the maximum light pulse range maybe different from frame to frame. This is shown in FIG. 7E, where thelight pulses are different from frame to frame. The sensor may be builtto be able to program different blanking times with a repeating patternof two or three or four or n frames. In FIG. 7E, four different lightpulses are illustrated, and Pulse 1 may repeat for example after Pulse 4and may have a pattern of four frames with different blanking times.This technique can be used to place the most powerful partition on thesmallest blanking time and therefore allow the weakest partition to havewider pulse on one of the next frames without the need of increasing thereadout speed. The reconstructed frame can still have a regular patternfrom frame to frame as it is constituted of many pulsed frames.

Referring now to FIGS. 8A and 8B, implementations of image sensors areillustrated. The image sensor illustrated in FIG. 8A is a traditionalimage sensor 800 including a pixel array common in the prior art. Theminimal area image sensor 820 illustrated in FIG. 8B is a pixel array inaccordance with the teachings and principles of the disclosure. Theminimal area image sensor 820 may be used in a distal tip of anendoscope. The distal tip of an endoscope is necessarily small becausethe distal tip is usually inserted in small areas such as body cavities.The distal tip of an endoscope is often too small to accommodate atraditional image sensor 800.

In a space-constrained environment such as the distal tip of anendoscope, it may be desirable to reduce non-sensitive portions of animage sensor to maximize the area of the image sensor that is devoted tolight sensing elements. This can reduce the total area of the imagesensor while preserving image quality. One implementation for reducingthe non-light sensing elements in the image sensor is to eliminate orreduce the number of optical black (“OB”) rows in the image sensor.However, eliminating the optical black rows can also eliminate thepossibility of implementing an OB-based column fixed pattern noisecancellation method that is commonly used in conventional imagingsystems. Column fixed pattern noise cancellation requires black pixeldata with typically 10 to 100 black pixels per column. The black pixelscorrect for a column-wise random offset prior to reading out lightsensing pixels. Disclosed herein are alternative methods, systems, anddevices for correcting for fixed pattern noise when using a minimal areaimage sensor 820.

Image sensors can incorporate special purpose, optically blind oroptical black (“OB”) rows and/or columns. Optical black pixels mayalternatively be referred to as manufacturing buffer pixels or dummypixels. An optical black row 804 is located at the top and/or bottom ofa record area 802. The record area 802 includes the imaging pixel array.An optical black column 806 is located to the right and/or left of thepixel array. The optical black rows and columns are used to offsetcalibration of the record area 802.

The example layout of the traditional image sensor 800 includes anoptical black row 804 on the top and bottom of the traditional recordarea 802. The traditional image sensor 800 further includes an opticalblack column 806 on the left and right sides of the record area 802. Theexample layout of the minimal area image sensor 820 includes opticalblack columns 806 on the left and right sides of the record area 802.The minimal area image sensor 820 does not include any optical blackrows 804. Each of the example embodiments may include a guard ring 808surrounding the circumference of the image sensor 800, 820.

The optical black rows 804 may be used to monitor the analog pixel blacklevel for purposes of an optical black clamp algorithm. The opticalblack rows 804 may also be used by a digital algorithm for the purposeof cancelling column fixed pattern noise (CFPN). The optical blackcolumns 806 may be used to assess the line offset as a means to cancelout line noise in the record area 802. Because line noise can betemporal, the line offset may be computed anew for each line of therecord area 802 in every frame.

The minimal area image sensor 820 provides an overall reduction in thesize of the image sensor by removing the optical black rows 804 from thetop and bottom sides of the record area 802. When deploying the minimalarea image sensor 820, the optical black columns 806 are used for theoptical black clamp algorithm rather than any optical black rows 804. Inan embodiment, all fixed pattern noise, including column fixed patternnoise, can be cancelled by acquiring frames of dark data. This negatesthe need for a dedicated CFPN correction and its associated opticalblack rows 804.

The number of optical black columns 806 might typically be 100 or moredepending on space constraints. The more optical black columns 806 thatare available, the greater the line-offset precision may be. Greaterprecision means lower line noise post-correction. Normally, allavailable physical optical black pixels are read for each line as shownin FIG. 9 . A further degree of pixel array size reduction can beachieved if, instead of having the requisite number of physical opticalblack pixels, (given a certain precision target), a smaller number ofphysical optical black pixels are implemented and the physical opticalblack pixels are resampled multiple times during the horizontal readoutprocess of the record area 802 and the optical black columns 806. Thisapproach is illustrated in FIG. 10 .

In an alternative embodiment, a minimal area image sensor includesoptical black rows 804 but does not include optical black columns 806.In such an embodiment, the optical black rows 804 may be read before andafter reading the active pixels in the record area 802 of the pixelarray.

The disclosures provided herein may be applied to all forms of fixedpattern noise and are not necessarily restricted to cancelling columnfixed pattern noise. Other types of fixed pattern noise may be cancelledby acquiring frames of dark data to negate the need for a dedicatedcolumn fixed pattern noise correction with its associated optical blackrows. In an embodiment, an off-sensor frame of memory is used forstoring each pixel's calibration data and subsequently cancelling allsources of fixed pattern noise at the pixel level. Although more memorymay be needed for a black frame calibration than for a column fixedpattern noise algorithm, there may be an advantage in that all sourcesof fixed pattern noise can be eliminated or significantly mitigated byway of the methods, systems, and devices disclosed herein. Examplesources of fixed pattern noise that can be eliminated or mitigated byway of the disclosures herein include column fixed pattern noise, pixelfixed pattern noise, and row fixed pattern noise.

FIG. 9 illustrates a readout sequence 908 for a pixel array common inthe prior art. As shown in FIG. 9 , the readout sequence 908 begins withcolumn readout 906 for each of the optical black columns 904. Theoptical black columns 904 may be similar to those optical black columns806 illustrated in FIGS. 8A and 8B. Upon completion of the columnreadout 906 for the optical black columns 904, the readout sequence 908begins the column readout 906 for the record area 910. The record area910 may be similar to the record area 802 illustrated in FIGS. 8A and8B. The record area 910 may include clear pixels 902 or color agnosticpixels. The readout sequence 908 continues until the entire record area910 has been read. After the record area 910 has been read, the opticalblack columns 904 on the opposite side are read. The readout sequence908 continues line-by-line until every row of the pixel array has beenread.

FIG. 10 illustrates a readout sequence 1008 for a pixel array having anarea size reduction that reduces the number of optical black pixels. Inthe readout sequence 1008 illustrated in FIG. 10 , the optical blackcolumns 1004 undergo column readout 1006 multiple times. As shown inFIG. 10 , the optical black column 1004 readout can be resampled m timeor n times. The record area may include clear pixels 1002.

Raw CMOS image sensor data present at the output of the digitizer may befar from ideal. It may often be the case that the optimal order withwhich to read out a horizontal row of pixels does not equate to theactual physical order within the array. Also, raw data often revealsundesirable artifacts that reflect the nature of the readoutarchitecture. These readout artifacts may include column fixed patternnoise arising from the variation in offset from column to column and mayfurther include temporal line noise resulting from circuit resetsassociated with the horizontal readout process.

Another property of CMOS (Complementary Metal Oxide Semiconductor)sensors is that a degree of dark signal may be generated by thephotodiode within the pixel. The amount of integrated signal arisingfrom dark signal depends on exposure time and temperature. Because thedark signal may be indistinguishable from photo-signal, changes in thedark signal translate to changes in signal pedestal in the analogdomain. Therefore, it may be important to sample and adjust for the darksignal so the available dynamic range of the analog to digital convertercan be fully exploited.

FIG. 11 is a graphical representation of a simple exponential smoothing(SES) pixel offset estimation with small and large values for w. SESpixel offset estimation can be implemented to reduce or eliminate fixedpattern noise in exposure frames.

Exponential smoothing is a timeseries forecasting method. Exponentialsmoothing results in a prediction that is a weighted sum of pastobservations, wherein the weights decay exponentially as pastobservations get older. In an embodiment, SES is used to generate areference frame based on a plurality of dark exposure frames. Each ofthe plurality of dark exposure frames is generated by the pixel arrayand includes dark frame data that is sensed when the emitter is notemitting electromagnetic radiation. The reference frame may be appliedto reduce fixed pattern noise in exposure frames and/or image framesgenerated by the image sensor. SES is used to increase the precision ofthe reference frame. In an embodiment, the SES algorithm explicitly usesan exponentially decreasing weight for factoring in previously captureddark exposure frames.

In an embodiment, SES is applied to dark frame data from a plurality ofdark exposure frames. SES is used to generate a reference frame based onthe dark frame data captured in the plurality of dark exposure frames.The reference frame does not include imaging data that is displayed on ascreen or otherwise provided to a user, and instead includes data thatis used to remove fixed pattern noise from exposure frames and/or imageframes. The reference frame is calculated by applying SES to theplurality of dark exposure frames. The plurality of dark exposure framesare captured over time and older dark exposure frames are given lessweight when calculating the reference frame. The reference frameincludes reference data that is subtracted from exposure frames and/orimage frames in furtherance of reducing fixed pattern noise. Each of theplurality of dark exposure frames is sensed by the pixel array when alight deficient environment is dark, and an emitter is not pulsingelectromagnetic radiation.

In an embodiment, an emitter emits pulses of electromagnetic radiationin a pattern that includes varying wavelengths of electromagneticradiation. In an embodiment, the pattern includes red, green, blue, andfluorescence wavelengths of electromagnetic radiation. The pattern mayfurther include instances wherein the emitter is not emittingelectromagnetic radiation. The pixel array can be configured to sensedark frame data when the emitter is not emitting electromagneticradiation. When the pixel array senses dark frame data, this results ina dark exposure frame. In an embodiment, the pattern of varyingwavelengths of electromagnetic radiation further includes instanceswherein the emitter is not emitting electromagnetic radiation. The pixelarray generates an exposure frame in response to each emission ofelectromagnetic radiation, and additionally generates a dark exposureframe in response to an instance wherein the emitter is not emittingelectromagnetic radiation. The exposure frames and dark exposure framesmay be captured in a repeating pattern over time such that the darkexposure frames are interspersed between (non-dark) exposure frames. Aseries of exposure frames may be combined to generate an image frame,and in an embodiment, there is a dark exposure frame corresponding witheach image frame or grouping of image frames. The series of darkexposure frames are used to generate a reference frame, and thereference frame is used to reduce the fixed pattern noise present in theexposure frames (and image frames). SES is applied to the series of darkexposure frames such that older dark exposure frames have lesser weightthan newer dark exposure frames.

In an embodiment, a single reference frame is incrementally adjustedeach time a dark exposure frame is sensed by the pixel array. Each pixelsample taken in the dark exposure frame is divided by an appropriatebinary number (2^(w)) before being added to the buffer content andmultiplied by (2^(w)−1)/2^(w). FIG. 11 graphically illustrates theimpact on the pixel offset estimate for small values of w and largevalues of w. As shown in FIG. 11 , high values of w result in greaterstatistical precision over time in a stable scenario. Lower values of wcause the SES correction to be more reactive to rapid changes at theexpense of precision and stability. In an embodiment, the value of w istunable via control registers in communication with the endoscopicsystem.

In an embodiment, dark current temperature dependence can be overcome byusing a running average calibration as described herein. In a rollingshutter operation, pixel integration time may be changed on aframe-to-frame basis to accommodate light environment changes controlledby an auto exposure algorithm. For example, the frame readout sequenceillustrated in FIGS. 3A-3D illustrate an electronic shutter beingadjusted within the frame to control integration time. Because thecalibration may be performed at a given integration time, the dark framecorrection algorithm may lose efficacy and become inaccurate when tryingto correct frames with different integration time. One implementation ofthe disclosure to overcome this issue is to introduce a secondcalibration point per pixel. This may require a second frame of memory.The second calibration point for each pixel may be collected at adifferent integration time. Pixel calibration data at a givenintegration time may be computed using linear interpolation. However,the use of linear interpolation can introduce interpolation error andcomplicate backend processing of the image data.

When pulsing light in a light deficient environment, the pixelintegration time may be substantially constant from frame to frame. Thisis illustrated especially in FIG. 3D, where light intensity is adjustedby changing the light pulse width or level. In this implementation, onlyone integration time calibration may be required, and interpolation maynot be needed. In an embodiment, dark frame subtraction can be used toadjust for the average offset of each pixel. This can suppress all formsof fixed pattern noise. Because the pixel offsets have temperaturedependence, the correction can be a running average process by takingsample dark frames at regular intervals and updating stored correctiondata based on the samples. The resultant quality of this correction maydepend on the sampling statistics.

In an embodiment, the uncertainty of a pixel offset estimate is equal tothe temporal noise of that pixel divided by the square root of thenumber of samples. This uncertainty may directly translate topost-correction pixel fixed pattern noise and is independent of theoriginal fixed pattern noise. In an embodiment where a video stream iscaptured at the rate of 60 image frames per second, the pixel fixedpattern noise may be less than one-fourth of the pixel temporal noise tobe imperceptible to a human viewer. The statistics for the perceptioncriterion depend only on pixel temporal noise as follows:

${PFPN}_{required} \leq \frac{\sigma_{T}}{4}$${PFPN}_{realized} = {\frac{\sigma_{T}}{\sqrt{N_{f}}}\therefore{N_{f} \geq {16}}}$

where σ_(T) is the pixel temporal noise. Therefore, the frame correctionprocess should be effective so long as there are at least 16 dark framesused to compute the average.

In an embodiment, SES capture on dark frames only is calculatedaccording to:

b_(i, j) = d_(i, j)(j = 0)$b_{i,j} = {{\frac{1}{2^{w}}d_{i,j}} + {\frac{\left( {2^{w} - 1} \right)}{2^{w}}{b_{i,{({j - 1})}}\left( {j > 0} \right)}}}$

where b_(i,j) is the dark frame correction buffer content for pixel i,following dark frame number j and d_(i,j) is the raw dark data for pixeli, taken from dark frame j. w is a tunable integer.

In an embodiment, SES is applied non-dark exposure frames according to:x′ _(i) =x _(i) −b _(i) +B

where x_(i) is the raw data input for pixel i in any non-dark frame andb_(i) is the current dark frame buffer content. x′_(i) is the output andB is the black clamp target level.

FIG. 12 is a graphical representation of a modulation of the simpleexponential smoothing (SES) index after a gain change. In an embodiment,the values of w are tunable via control registers in communication withthe endoscopic system. The value of w may be automatically adjusted toensure corrections are reactive at startup, when T_(J) is changing mostdramatically, or in certain embodiments following changes in exposuretime. For example, if a large change in gain or exposure time occurs,the value of w can be lowered and then restored to a baselineincrementally from frame to frame. The incremental adjustments can varylinearly or in a roughly exponential manner as shown in FIG. 12 .

FIG. 13 is a schematic diagram of a process flow 1300 for cancellationof fixed pattern noise. The process flow 1300 includes sampling at 1302the first pixel and resetting the frame buffer to zero. The process flow1300 includes determining at 1304 whether the sampled pixel is a darkpixel (may be referred to as an optical black pixel). If it isdetermined at 1304 that the sampled pixel is a dark pixel, then theprocess flow 1300 includes determining at 1306 whether the buffer forthe pixel is zero. If it is determined at 1306 that the buffer for thepixel dark pixel is zero, then the pixel value is written at 1308directly to the buffer location for the dark pixel. The next pixel issampled at 1310. If it is determined at 1306 that the buffer for thedark pixel is not equal to zero, then the buffer location for the darkpixel is read at 1314 and multiplied by

$\frac{\left( {2^{w} - 1} \right)}{2^{w}}.$The result is added to the new pixel sample and divided by 2^(w) andthen written back to the buffer. The next pixel is sampled at 1310.

If it is determined at 1304 that the sampled pixel is not a dark pixel,then the process flow 1300 includes reading the buffer for the active(non-dark) pixel at 1312 and subtracting content from the data. Theprocess flow 1300 may further including adding constant black level ifrequired. The next pixel is sampled at 1310.

FIG. 14 illustrates a process flow 1400 to be implemented by acontroller and/or monochrome image signal processor (ISP) for generatinga video stream having RGB images with fluorescence data overlaidthereon. The image signal processor (ISP) chain may be assembled for thepurpose of generating sRGB image sequences from raw sensor data, yieldedin the presence of the G-R-G-B-Fluorescence light pulsing scheme. In theprocess flow 1400, the first stage is concerned with making corrections(see receiving data from the sensor at 1402, re-ordering at 1404, andsensor corrections at 1406 in FIG. 14 ) to account for anynon-idealities in the sensor technology for which it is most appropriateto work in the raw data domain. At the next stage, multiple frames (forexample, a green frame 1408 a, a red-blue frame 1408 b, and afluorescence frame 1408 c) are buffered because each final frame derivesdata from multiple raw frames. The frame reconstruction at 1264 proceedsby sampling data from a current frame and two buffered frames (see 1408a, 1408 b, and/or 1408 c). The reconstruction process results in fullcolor frames in linear RGB color space that include fluorescence imagedata. In this example, the white balance coefficients at 1418 and colorcorrection matrix at 1420 are applied before converting to YCbCr spaceat 1422 for subsequent edge enhancement at 1424. After edge enhancementat 1424, images are transformed back to linear RGB at 1426 for scalingat 1428, if applicable. Finally, the gamma transfer function at 1430 isapplied to translate the data into the sRGB domain at 1432.

FIG. 15 is an example of color fusion hardware 1500. The color fusionhardware 1500 stores in memory 1504 an R-G-B-G-Fluorescence video datastream with a memory writer 1502 and converts the video data stream to aparallel RGB+Fluorescence video data stream at 1505. The bit width onthe input side may be, e.g., 12 bits per color. The output width forthat example would be at least 36 bits per pixel. Other embodiments mayhave different initial bit widths and 3+ times that number for theoutput width. The memory writer 1502 block takes as its input theRGBG-Fluorescence video stream and writes each frame to its correctframe memory 1504 (the memory writer triggers off the same pulsegenerator (see 2510) that runs the laser light source). The memory 1504may store exposure frame data in a pattern such as the one illustrated,namely: Red, Green 1, Blue, Green 2, Fluorescence and then starts backwith Red again. The memory reader 1506 reads three frames at once toconstruct an RGB pixel. Each pixel is three times the bit width of anindividual color component. The memory reader 1506 also triggers off thelaser pulse generator at 2510. In an embodiment, the memory reader 1506waits until Red, Green 1 and Blue frames have been written, thenproceeds to read them out in parallel while the writer continues writingGreen 2, Fluorescence, and starts back on Red. When Red completes thereader begins reading from Blue, Green 2, Fluorescence, and Red. Thispattern continues indefinitely.

FIG. 16 is a schematic diagram of a process flow 1600 for sensorcorrection processes. The process flow 1600 is an example implementationof the front end of an image signal process that has been developed inthe context of a system incorporating a minimal area image sensor. Inthe example process flow 1600, there are two digitizers on the sensorconverting the even and odd-numbered columns respectively andtransmitting serial data on two differential ports. The process flow1600 may be employed in a color and fluorescence pulsed system asdiscussed herein. The process flow 1600 may be employed to counteractnon-idealities in CMOS image sensors such as fixed pattern noise (FPN)and line noise. Fixed pattern noise is a dispersion in the offsets ofthe sense elements. Typically, most of the FPN is a pixel to pixeldispersion which stems from random variations in dark current fromphotodiode to photodiode. The systems disclosed herein maintain completecontrol of the illumination source, and this enables dark data to beacquired and used to correct for the pixel and column offsets. In theillustrated example, a single frame buffer may be used to make a runningaverage of the whole frame without light using, e.g., simple exponentialsmoothing. This dark average frame may be subtracted from everyilluminated frame during regular operation. Line noise is a stochastictemporal variation in the offsets of pixels within each row. Becauseline noise is temporal, the correction is computed for each line andeach frame. For this purpose, there are usually many optically blind(OB) pixels within each row in a pixel array. The OB pixels must firstbe sampled to assess the line offset before sampling the light sensitivepixels. The line offset is then subtracted during the line noisecorrection process.

The process flow 1600 includes performing top deserialization 1602 andbottom deserialization 1603. The process flow 1600 includes performingline reordering at the top port at 1604 and line reordering at thebottom port at 1605. The information may be stored in separate databases1632, 1634 or other memory devices upon the completion of linereordering. The process flow 1600 includes performing a black clampcalculation on the top ADC at 1606 and a black clamp calculation on thebottom ADC at 1607. The information exits the process flow 1600 on afirst-in-first-out (FIFO) basis. The process flow 1600 includesperforming line noise correction at the top ADC at 1608 and line noisecorrection at the bottom ADC at 1609. The process flow 1600 includesperforming full line recombination at 1610 and dark frame accumulationat 1612. The information may be stored in a database 1630 or othermemory device before fixed pattern noise (FPN) correction is performed.The process flow includes performing fixed pattern noise (FPN)correction at 1614 and pixel defect correction at 1616. The process flow1600 includes performing programmable digital gain at 1618 before avideo stream exits the process flow 1600 to be provided to a user.

Individual optical black pixels which do not behave normally may badlydegrade the quality of the black offset measurements. An approachdisclosed herein includes computing the media of a group of five pixelsfor each optical black pixel. The five pixels include the pixel inquestion and its four nearest neighbors. The final line offset estimatemay then be computed as the mean of all the medians. In an embodiment,some provisions are made to avoid losing statistics at the beginning andthe end. Such provisions include buffering the whole sample of opticalblacks and wrapping around the sample of five. Buffering necessitatespipelining the data and results in a delay equal to at least the totalnumber of optical blacks per analog to digital converter channel, perrow.

The line offset estimate for an even channel (assuming two analog todigital converters with odd-even interspersion), row # r can be computedas follows:

$L_{r,{even}} = \frac{2 \cdot {\sum_{{i = 0},2,{4\mspace{14mu}\ldots}}^{N_{OB} - 2}\mu_{i}}}{N_{OB}}$

The line offset where N_(OB) may be the total number of optical blackpixels per row and μ_(i) may be the median for optical black pixel i,computed thus:

μ₀ = median[x_((N_(OB) − 4)), x_((N_(OB) − 2)), x₀, x₂, x₄]μ₂ = median[x_((N_(OB) − 2)), x₀, x₂, x₄, x₆]μ₄ = median[x₀, x₂, x₄, x₆, x₈] …μ_((N_(OB) − 2)) = median[x_((N_(OB) − 6)), x_((N_(OB) − 4)), x_((N_(OB) − 2)), x₀, x₂]

Likewise, the line offset estimate for an odd channel (assuming twoanalog to digital converters with odd-even interspersion), row # r canbe computed as follows:

$L_{r,{odd}} = \frac{2 \cdot {\sum_{{i = 1},3,{5\mspace{14mu}\ldots}}^{N_{OB} - 1}\mu_{i}}}{N_{OB}}$where

μ₁ = median[x_((N_(OB) − 3)), x_((N_(OB) − 1)), x₁, x₃, x₅]μ₃ = median[x_((N_(OB) − 1)), x₁, x₃, x₅, x₇]μ₅ = median[x₁, x₃, x₅, x₇, x₉] …μ_((N_(OB) − 1)) = median[x_((N_(OB) − 5)), x_((N_(OB) − 3)), x_((N_(OB) − 1)), x₁, x₃]

The overall frame black level may be computed by accumulating each ofthe line offsets to compute the overall black level. In this approach,the overall black level is determined using simple exponential smoothing(SES). Simple exponential smoothing allows the rows at the end of theframe to have a greater influence on the final black estimate. This maybe desirable in certain implementations for addressing changes in blackoffset occurring on sub-frame timescales. The simple exponentialsmoothing algorithm determines a running estimate that may beincrementally adjusted each time a sample is made available. Forconvenience the sample can be divided by a binary number (2^(q)) beforebeing added to the previous estimate. The previous estimate may be firstmultiplied by (2^(q)−1)/2^(q) each time, in order to normalize theresult. High values of q result in greater statistical precision overtime in a stable scenario. Lower values of q may make the correctionmore reactive to rapid changes. q should be made available as a tunableparameter. This may be computed as follows:

k_(r) = L_(r)(r = 0)$k_{r} = {{\frac{1}{2^{q}}L_{r}} + {\frac{\left( {2^{q} - 1} \right)}{2^{q}}{k_{({r - 1})}\left( {r > 0} \right)}}}$where k_(r) is the black level estimate after row r and L_(r) may be theline offset estimate for row r. The decision about what to do with theblack clamp digital to analog converters may be made after the final rowin the array has been added.

The black clamp algorithm at 1606, 1607 may require a target blacklevel, and this can be provided by an adjustable parameter. The blackclamp digital to analog converter on the sensor for the channel inquestion would be pushed up or down depending on whether the observedblack estimate may be above or below the target. The size of the pushcould be the smallest unit, i.e. one digital to analog converter count,provided the black offset may be close to the target. In the case thatthe black level may be a long way from the target, a larger proportionalpush could be made. The algorithm would need to know a rough calibrationof the correspondence between black clamp digital to analog convertercounts and sensor analog to digital converter counts and thedirectionality of digital to analog converter adjustments with respectto the output black level.

The line noise is corrected at 1608 and 1609. Line noise refers tostochastic, temporal variations in the offset of a horizontal row ofpixels. There may be multiple sources, but it can be considered as resetnoise arising from analog elements being reset each time a row of pixelsis read out. It may be temporal, and a new correction should be computedfor each new line per every frame. Since the amplification stage at theanalog to digital converter input may be the final analog element, theremay be good reason to suspect that the line noise appearsphenomenologically independent per analog to digital converter channel.One approach is to correct each analog to digital converter channelseparately.

It can be challenging to completely eliminate line noise because thesample of optical black pixels used for the line offset estimate may beseparate from the sample to which the correction may be applied. Thesample statistics are finite. Assuming the noise is Gaussian, thepost-correction line noise may be approximately equal to the uncertaintyin the line offset estimate arising from the pixel temporal noisepresent in the optical black pixels:

$\sigma_{L,{post}} \approx \frac{\sigma_{P}}{\sqrt{N_{OB}}}$where σ_(L,post) is the post correction temporal line noise, σ_(p) isoptical black pixel temporal noise, and N_(OB) is the number of opticalblack pixels. The line noise correction also introduces a spatial linenoise component, mostly as a consequence of the pixel fixed patternnoise present within the optical black pixels:

${FPN}_{L,{post}} \approx \frac{{FPN}_{P}}{\sqrt{N_{OB}}}$

This artifact can be eliminated by the fixed pattern noise correctionlater in the chain. Simulations have indicated that in order fortemporal line noise to be invisible, the magnitude should be less thanapproximately 1/10 of the pixel temporal noise.

Line-noise correction application to optically sighted (clear) pixels:x′ _(i) =x _(i) −L+Bwhere L is the line offset estimate for the current line, ported fromthe ‘Black Clamp’ module and B is the black clamp target level.

Full line recombination at 1610 includes combining the two data channels(i.e., the top data channel and the bottom data channel) into a fullline. The top and bottom data channels need to be interleaved in such away that the final clear pixel order reflects the correct order in thearray.

The fixed pattern noise correction at 1614 includes adjusting a runningoffset estimate on a per physical pixel basis. CMOS image sensors havemultiple noise sources. The magnitude and appearance of noise depends ona range of physical conditions. Pure Poisson or Gaussian temporal noisewith no coherent components (e.g. photon shot noise or source follower1/f read noise) looks as natural as noise can look. All otherperceivable noise types may degrade the image quality to a greaterextent for the same amplitude. Spatial noise (fixed pattern noise) maybe especially damaging and CMOS sensors inherently have at least twosources. CMOS image sensors experience pixel fixed pattern noise andcolumn fixed pattern noise. The pixel fixed pattern noise may be mostlydue to variations in photodiode leakage current (dark signal) from pixelto pixel (DSNU). This source may be exponentially dependent on junctiontemperature (T_(J)) and linearly dependent on exposure time. Columnfixed pattern noise may be a consequence of the readout architecture, inwhich pixels from within the same column are channeled through commonanalog readout elements.

Typically, an on-chip digital fixed pattern noise correction involvesdealing only with the column fixed pattern noise component and requiresone offset correction register per column. The precision of such acorrection might typically be 20 bits or so per column, which translatesto around 5 kB of RAM for a 1920×1080 array. One of the benefits ofmigrating the digital sensor corrections to the image signal processormay be the ready availability of RAM. This opens up the possibility of acomprehensive fixed pattern noise correction which cancels out any row,column or pixel-wise component. This may be accomplished by means ofsimple exponential smoothing (SES) in which each fresh dark frame samplemay be used to adjust a running offset estimate on a per physical pixelbasis.

The programmable digital gain 1618 may be executed by a programmabledigital amplifier. CMOS image sensors are usually equipped with digitalprogrammable gain stages with very fine increments. This may be tofacilitate auto exposure processes which typically modulate the gain andthe exposure time. The programmable digital amplifier can be used toalign the range of the sensor analog to digital converter to the rangeof the image signal processor (e.g. ×2 for 11 bit analog to digitalconverter to 12-bit image signal processor). A small amount of digitalgain may also be used to trim off the imprint of the digital line noiseand fixed pattern noise corrections which becomes apparent at the fullrange of the analog to digital converter.

A more space conservative approach involves combining large amounts ofcontrol RAM into single, long registers. In the extreme case, allparameters could be placed into a single register, requiring no addressROM. This solution may be not very practical because writing controlregisters takes time and typical video applications involve changing asmall number of operational parameters on a frame-by-frame basis. Themost practical solution may be afforded by concatenating functionallyrelated sets of parameters into a small number of long registers. Thedifference in space implied by having ten registers (requiring 4 addressbits) versus one may be negligible. In particular it makes sense thatall of the parameters which are written periodically at a high ratebelong together in an exclusive register (the frame register), in orderto keep the time required to write it to a minimum. Such parametersinclude the exposure times, gains, incremental offset adjustments andany others necessary to maintain continuous high-quality video. If thedigital data-path logic has been migrated off chip as described earlier,the black clamp voltage adjustment data also belongs in such a registersince it should be revised every frame too. In an implementation, duringthis configuration phase can registers be written and therefore thetiming of the frame register writes with respect to the overall frametiming should be carefully controlled by the camera.

Other examples of parametric register groupings could include; analogcurrents, analog voltages, pixel timing, vertical timing, sensorcommands (resets etc.) and so on. In FIG. 15 , the arrangement ofregisters may be shown for a specific minimal-area sensor design. The“Command” register may be used for top level event-oriented 1-bitcommands such as chip resets and the loads for the other registers shownbelow it. A 2-wire protocol address decoder decides which shift registerto direct incoming 2-wire protocol data toward. To load the “Format”register, e.g., the external controller sends a command with the addressassociated with the Format register. This places the stream of data intothe Format-register shift register. Then in order to latch the data, afollow up command may be sent to the Command register with theparticular “load Format” bit set. It will be appreciated that aplurality of control registers may be used. The control registers may bedigital latches that may be loaded via shift registers. The shiftregisters may be arbitrary in length. In an embodiment, a majority ofthe plurality of control registers may be loaded using shift registersthat include many tens of bits. In an embodiment, a majority of theplurality of control registers may be loaded using shift registers thatinclude hundreds of bits. In an embodiment, a majority of the pluralityof control registers may be loaded using shift registers that includethousands of bits. In an embodiment, the shift registers may be loadedusing a serial, 2-wire protocol. In an embodiment, one of the shiftregisters may be dedicated to frame-to-frame parameter changes, such as,e.g., integration times and black clamp offset adjustments.

FIG. 17 is a schematic diagram of a pattern reconstruction process. Theexample pattern illustrated in FIG. 17 includes Red, Green, Blue, andFluorescence pulses of light that each last a duration of T1. In variousembodiments, the pulses of light may be of the same duration or ofdiffering durations. The Red, Green, Blue, and Fluorescence exposureframes are combined to generate an RGB image with fluorescence dataoverlaid thereon. A single image frame comprising a red exposure frame,a green exposure frame, a blue exposure frame, and a fluorescenceexposure frame requires a time period of 4*T1 to be generated. The timedurations shown in FIG. 17 are illustrative only and may vary fordifferent implementations. In other embodiments, different pulsingschemes may be employed. For example, embodiments may be based on thetiming of each color component or frame (T1) and the reconstructed framehaving a period twice that of the incoming color frame (2×T1). Differentframes within the sequence may have different frame periods and theaverage capture rate could be any multiple of the final frame rate.

In an embodiment, the dynamic range of the system is increased byvarying the pixel sensitivities of pixels within the pixel array of theimage sensor. Some pixels may sense reflected electromagnetic radiationat a first sensitivity level, other pixels may sense reflectedelectromagnetic radiation at a second sensitivity level, and so forth.The different pixel sensitivities may be combined to increase thedynamic range provided by the pixel configuration of the image sensor.In an embodiment, adjacent pixels are set at different sensitivitiessuch that each cycle includes data produced by pixels that are more andless sensitive with respect to each other. The dynamic range isincreased when a plurality of sensitivities are recorded in a singlecycle of the pixel array. In an embodiment, wide dynamic range can beachieved by having multiple global TX, each TX firing only on adifferent set of pixels. For example, in global mode, a global TX1signal is firing a set 1 of pixels, a global TX2 signal is firing a set2 of pixel, a global TXn signal is firing a set n of pixels, and soforth.

FIGS. 18A-18C each illustrate a light source 1800 having a plurality ofemitters. The emitters include a first emitter 1802, a second emitter1804, and a third emitter 1806. Additional emitters may be included, asdiscussed further below. The emitters 1802, 1804, and 1806 may includeone or more laser emitters that emit light having different wavelengths.For example, the first emitter 1802 may emit a wavelength that isconsistent with a blue laser, the second emitter 1804 may emit awavelength that is consistent with a green laser, and the third emitter1806 may emit a wavelength that is consistent with a red laser. Forexample, the first emitter 1802 may include one or more blue lasers, thesecond emitter 1804 may include one or more green lasers, and the thirdemitter 1806 may include one or more red lasers. The emitters 1802,1804, 1806 emit laser beams toward a collection region 1808, which maybe the location of a waveguide, lens, or other optical component forcollecting and/or providing light to a waveguide, such as the jumperwaveguide 206 or lumen waveguide 210 of FIG. 2 .

In an implementation, the emitters 1802, 1804, and 1806 emithyperspectral wavelengths of electromagnetic radiation. Certainhyperspectral wavelengths may pierce through tissue and enable a medicalpractitioner to “see through” tissues in the foreground to identifychemical processes, structures, compounds, biological processes, and soforth that are located behind the tissues in the foreground. Thehyperspectral wavelengths may be specifically selected to identify aspecific disease, tissue condition, biological process, chemicalprocess, type of tissue, and so forth that is known to have a certainspectral response.

In an implementation where a patient has been administered a reagent ordye to aid in the identification of certain tissues, structures,chemical reactions, biological processes, and so forth, the emitters1802, 1804, and 1806 may emit wavelength(s) for fluorescing the reagentsor dyes. Such wavelength(s) may be determined based on the reagents ordyes administered to the patient. In such an embodiment, the emittersmay need to be highly precise for emitting desired wavelength(s) tofluoresce or activate certain reagents or dyes.

In an implementation, the emitters 1802, 1804, and 1806 emit a laserscanning pattern for mapping a topology of a scene and/or forcalculating dimensions and distances between objects in the scene. In anembodiment, the endoscopic imaging system is used in conjunction withmultiple tools such as scalpels, retractors, forceps, and so forth. Insuch an embodiment, each of the emitters 1802, 1804, and 1806 may emit alaser scanning pattern such that a laser scanning pattern is projectedon to each tool individually. In such an embodiment, the laser scanningdata for each of the tools can be analyzed to identify distances betweenthe tools and other objects in the scene.

In the embodiment of FIG. 18B, the emitters 1802, 1804, 1806 eachdeliver laser light to the collection region 1808 at different angles.The variation in angle can lead to variations where electromagneticenergy is located in an output waveguide. For example, if the lightpasses immediately into a fiber bundle (glass or plastic) at thecollection region 1808, the varying angles may cause different amountsof light to enter different fibers. For example, the angle may result inintensity variations across the collection region 1808. Furthermore,light from the different emitters may not be homogenously mixed so somefibers may receive different amounts of light of different colors.Variation in the color or intensity of light in different fibers canlead to non-optimal illumination of a scene. For example, variations indelivered light or light intensities may result at the scene andcaptured images.

In one embodiment, an intervening optical element may be placed betweena fiber bundle and the emitters 1802, 1804, 1806 to mix the differentcolors (wavelengths) of light before entry into the fibers or otherwaveguide. Example intervening optical elements include a diffuser,mixing rod, one or more lenses, or other optical components that mix thelight so that a given fiber receive a same amount of each color(wavelength). For example, each fiber in the fiber bundle may have asame color. This mixing may lead to the same color in each fiber butmay, in some embodiments, still result in different total brightnessdelivered to different fibers. In one embodiment, the interveningoptical element may also spread out or even out the light over thecollection region so that each fiber carries the same total amount oflight (e.g., the light may be spread out in a top hat profile). Adiffuser or mixing rod may lead to loss of light.

Although the collection region 1808 is represented as a physicalcomponent in FIG. 18A, the collection region 1808 may simply be a regionwhere light from the emitters 1802, 1804, and 1806 is delivered. In somecases, the collection region 1808 may include an optical component suchas a diffuser, mixing rod, lens, or any other intervening opticalcomponent between the emitters 1802, 1804, 1806 and an output waveguide.

FIG. 18C illustrates an embodiment of a light source 1800 with emitters1802, 1804, 1806 that provide light to the collection region 1808 at thesame or substantially same angle. The light is provided at an anglesubstantially perpendicular to the collection region 1808. The lightsource 1800 includes a plurality of dichroic mirrors including a firstdichroic mirror 1810, a second dichroic mirror 1812, and a thirddichroic mirror 1814. The dichroic mirrors 1810, 1812, 1814 includemirrors that reflect a first wavelength of light but transmit (or aretransparent to) a second wavelength of light. For example, the thirddichroic mirror 1814 may reflect blue laser light provided by the thirdemitter, while being transparent to the red and green light provided bythe first emitter 1802 and the second emitter 1804, respectively. Thesecond dichroic mirror 1812 may be transparent to red light from thefirst emitter 1802, but reflective to green light from the secondemitter 1804. If other colors or wavelengths are included dichroicmirrors may be selected to reflect light corresponding to at least oneemitter and be transparent to other emitters. For example, the thirddichroic mirror 1814 reflect the light form the third emitter 1806 butis to emitters “behind” it, such as the first emitter 1802 and thesecond emitter 1804. In embodiments where tens or hundreds of emittersare present, each dichroic mirror may be reflective to a correspondingemitter and emitters in front of it while being transparent to emittersbehind it. This may allow for tens or hundreds of emitters to emitelectromagnetic energy to the collection region 1808 at a substantiallysame angle.

Because the dichroic mirrors allow other wavelengths to transmit or passthrough, each of the wavelengths may arrive at the collection region1808 from a same angle and/or with the same center or focal point.Providing light from the same angle and/or same focal/center point cansignificantly improve reception and color mixing at the collectionregion 1808. For example, a specific fiber may receive the differentcolors in the same proportions they were transmitted/reflected by theemitters 1802, 1804, 1806 and mirrors 1810, 1812, 1814. Light mixing maybe significantly improved at the collection region compared to theembodiment of FIG. 18B. In one embodiment, any optical componentsdiscussed herein may be used at the collection region 1808 to collectlight prior to providing it to a fiber or fiber bundle.

FIG. 18C illustrates an embodiment of a light source 1800 with emitters1802, 1804, 1806 that also provide light to the collection region 1808at the same or substantially same angle. However, the light incident onthe collection region 1808 is offset from being perpendicular. Angle1816 indicates the angle offset from perpendicular. In one embodiment,the laser emitters 1802, 1804, 1806 may have cross sectional intensityprofiles that are Gaussian. As discussed previously, improveddistribution of light energy between fibers may be accomplished bycreating a more flat or top-hat shaped intensity profile. In oneembodiment, as the angle 1816 is increased, the intensity across thecollection region 1808 approaches a top hat profile. For example, atop-hat profile may be approximated even with a non-flat output beam byincreasing the angle 1816 until the profile is sufficiently flat. Thetop hat profile may also be accomplished using one or more lenses,diffusers, mixing rods, or any other intervening optical componentbetween the emitters 1802, 1804, 1806 and an output waveguide, fiber, orfiber optic bundle.

FIG. 19 is a schematic diagram illustrating a single optical fiber 1902outputting via a diffuser 1904 at an output. In one embodiment, theoptical fiber 1902 has a diameter of 500 microns, a numerical apertureof 0.65, and emits a light cone 1906 of about 70 or 80 degrees without adiffuser 1904. With the diffuser 1904, the light cone 1906 may have anangle of about 110 or 120 degrees. The light cone 1906 may be a majorityof where all light goes and is evenly distributed. The diffuser 1904 mayallow for more even distribution of electromagnetic energy of a sceneobserved by an image sensor.

In one embodiment, the lumen waveguide 210 includes a single plastic orglass optical fiber of about 500 microns. The plastic fiber may be lowcost, but the width may allow the fiber to carry a sufficient amount oflight to a scene, with coupling, diffusion, or other losses. Forexample, smaller fibers may not be able to carry as much light or poweras a larger fiber. The lumen waveguide 210 may include a single or aplurality of optical fibers. The lumen waveguide 210 may receive lightdirectly from the light source or via a jumper waveguide. A diffuser maybe used to broaden the light output 206 for a desired field of view ofthe image sensor 214 or other optical components.

Although three emitters are shown in FIGS. 18A-18C, emitters numberingfrom one into the hundreds or more may be used in some embodiments. Theemitters may have different wavelengths or spectrums of light that theyemit, and which may be used to contiguously cover a desired portion ofthe electromagnetic spectrum (e.g., the visible spectrum as well asinfrared and ultraviolet spectrums). The emitters may be configured toemit visible light such as red light, green light, and blue light, andmay further be configured to emit hyperspectral emissions ofelectromagnetic radiation, fluorescence excitation wavelengths forfluorescing a reagent, and/or laser mapping patterns for calculatingparameters and distances between objects in a scene.

FIG. 20 illustrates a portion of the electromagnetic spectrum 2000divided into twenty different sub-spectrums. The number of sub-spectrumsis illustrative only. In at least one embodiment, the spectrum 2000 maybe divided into hundreds of sub-spectrums, each with a small waveband.The spectrum may extend from the infrared spectrum 2002, through thevisible spectrum 2004, and into the ultraviolet spectrum 2006. Thesub-spectrums each have a waveband 2008 that covers a portion of thespectrum 2000. Each waveband may be defined by an upper wavelength and alower wavelength.

Hyperspectral imaging incudes imaging information from across theelectromagnetic spectrum 2000. A hyperspectral pulse of electromagneticradiation may include a plurality of sub-pulses spanning one or moreportions of the electromagnetic spectrum 2000 or the entirety of theelectromagnetic spectrum 2000. A hyperspectral pulse of electromagneticradiation may include a single partition of wavelengths ofelectromagnetic radiation. A resulting hyperspectral exposure frameincludes information sensed by the pixel array subsequent to ahyperspectral pulse of electromagnetic radiation. Therefore, ahyperspectral exposure frame may include data for any suitable partitionof the electromagnetic spectrum 2000 and may include multiple exposureframes for multiple partitions of the electromagnetic spectrum 2000. Inan embodiment, a hyperspectral exposure frame includes multiplehyperspectral exposure frames such that the combined hyperspectralexposure frame comprises data for the entirety of the electromagneticspectrum 2000.

In one embodiment, at least one emitter (such as a laser emitter) isincluded in a light source (such as the light sources 202, 1800) foreach sub-spectrum to provide complete and contiguous coverage of thewhole spectrum 2000. For example, a light source for providing coverageof the illustrated sub-spectrums may include at least 20 differentemitters, at least one for each sub-spectrum. In one embodiment, eachemitter covers a spectrum covering 40 nanometers. For example, oneemitter may emit light within a waveband from 500 nm to 540 nm whileanother emitter may emit light within a waveband from 540 nm to 580 nm.In another embodiment, emitters may cover other sizes of wavebands,depending on the types of emitters available or the imaging needs. Forexample, a plurality of emitters may include a first emitter that coversa waveband from 500 to 540 nm, a second emitter that covers a wavebandfrom 540 nm to 640 nm, and a third emitter that covers a waveband from640 nm to 650 nm. Each emitter may cover a different slice of theelectromagnetic spectrum ranging from far infrared, mid infrared, nearinfrared, visible light, near ultraviolet and/or extreme ultraviolet. Insome cases, a plurality of emitters of the same type or wavelength maybe included to provide sufficient output power for imaging. The numberof emitters needed for a specific waveband may depend on the sensitivityof a monochrome sensor to the waveband and/or the power outputcapability of emitters in that waveband.

The waveband widths and coverage provided by the emitters may beselected to provide any desired combination of spectrums. For example,contiguous coverage of a spectrum using very small waveband widths(e.g., 10 nm or less) may allow for highly selective hyperspectraland/or fluorescence imaging. The waveband widths may allow forselectively emitting the excitation wavelength(s) for one or moreparticular fluorescent reagents. Additionally, the waveband widths mayallow for selectively emitting certain partitions of hyperspectralelectromagnetic radiation for identifying specific structures, chemicalprocesses, tissues, biological processes, and so forth. Because thewavelengths come from emitters which can be selectively activated,extreme flexibility for fluorescing one or more specific fluorescentreagents during an examination can be achieved. Additionally, extremeflexibility for identifying one or more objects or processes by way ofhyperspectral imaging can be achieved. Thus, much more fluorescenceand/or hyperspectral information may be achieved in less time and withina single examination which would have required multiple examinations,delays because of the administration of dyes or stains, or the like.

FIG. 21 is a schematic diagram illustrating a timing diagram 2100 foremission and readout for generating an image. The solid line representsreadout (peaks 2102) and blanking periods (valleys) for capturing aseries of exposure frames 2104-2114. The series of exposure frames2104-2114 may include a repeating series of exposure frames which may beused for generating laser scanning, hyperspectral, and/or fluorescencedata that may be overlaid on an RGB video stream. In an embodiment, asingle image frame comprises information from multiple exposure frames,wherein one exposure frame includes red image data, another exposureframe includes green image data, and another exposure frame includesblue image data. Additionally, the single image frame may include one ormore of hyperspectral image data, fluorescence image data, and laserscanning data. The multiple exposure frames are combined to produce thesingle image frame. The single image frame is an RGB image withhyperspectral imaging data. The series of exposure frames include afirst exposure frame 2104, a second exposure frame 2106, a thirdexposure frame 2108, a fourth exposure frame 2110, a fifth exposureframe 2112, and an Nth exposure frame 2126.

Additionally, the hyperspectral image data, the fluorescence image data,and the laser scanning data can be used in combination to identifycritical tissues or structures and further to measure the dimensions ofthose critical tissues or structures. For example, the hyperspectralimage data may be provided to a corresponding system to identify certaincritical structures in a body such as a nerve, ureter, blood vessel,cancerous tissue, and so forth. The location and identification of thecritical structures may be received from the corresponding system andmay further be used to generate topology of the critical structuresusing the laser scanning data. For example, a corresponding systemdetermines the location of a cancerous tumor based on hyperspectralimaging data. Because the location of the cancerous tumor is known basedon the hyperspectral imaging data, the topology and distances of thecancerous tumor may then be calculated based on laser scanning data.This example may also apply when a cancerous tumor or other structure isidentified based on fluorescence imaging data.

In one embodiment, each exposure frame is generated based on at leastone pulse of electromagnetic energy. The pulse of electromagnetic energyis reflected and detected by an image sensor and then read out in asubsequent readout (2102). Thus, each blanking period and readoutresults in an exposure frame for a specific spectrum of electromagneticenergy. For example, the first exposure frame 2104 may be generatedbased on a spectrum of a first one or more pulses 2116, a secondexposure frame 2106 may be generated based on a spectrum of a second oneor more pulses 2118, a third exposure frame 2108 may be generated basedon a spectrum of a third one or more pulses 2120, a fourth exposureframe 2110 may be generated based on a spectrum of a fourth one or morepulses 2122, a fifth exposure frame 2112 may be generated based on aspectrum of a fifth one or more pulses 2124, and an Nth exposure frame2126 may be generated based on a spectrum of an Nth one or more pulses2126.

The pulses 2116-2126 may include energy from a single emitter or from acombination of two or more emitters. For example, the spectrum includedin a single readout period or within the plurality of exposure frames2104-2114 may be selected for a desired examination or detection of aspecific tissue or condition. According to one embodiment, one or morepulses may include visible spectrum light for generating an RGB or blackand white image while one or more additional pulses are emitted to sensea spectral response to a fluorescence wavelength of electromagneticradiation. For example, pulse 2116 may include red light, pulse 2118 mayinclude blue light, and pulse 2120 may include green light while theremaining pulses 2122-2126 may include wavelengths and spectrums fordetecting a specific tissue type, fluorescing a reagent, and/or mappingthe topology of the scene. As a further example, pulses for a singlereadout period include a spectrum generated from multiple differentemitters (e.g., different slices of the electromagnetic spectrum) thatcan be used to detect a specific tissue type. For example, if thecombination of wavelengths results in a pixel having a value exceedingor falling below a threshold, that pixel may be classified ascorresponding to a specific type of tissue. Each frame may be used tofurther narrow the type of tissue that is present at that pixel (e.g.,and each pixel in the image) to provide a very specific classificationof the tissue and/or a state of the tissue (diseased/healthy) based on aspectral response of the tissue and/or whether a fluorescent reagent ispresent at the tissue.

The plurality of frames 2104-2114 is shown having varying lengths inreadout periods and pulses having different lengths or intensities. Theblanking period, pulse length or intensity, or the like may be selectedbased on the sensitivity of a monochromatic sensor to the specificwavelength, the power output capability of the emitter(s), and/or thecarrying capacity of the waveguide.

In one embodiment, dual image sensors may be used to obtainthree-dimensional images or video feeds. A three-dimensional examinationmay allow for improved understanding of a three-dimensional structure ofthe examined region as well as a mapping of the different tissue ormaterial types within the region.

In an example implementation, a fluorescent reagent is provided to apatient, and the fluorescent reagent is configured to adhere tocancerous cells. The fluorescent reagent is known to fluoresce whenradiated with a specific partition of electromagnetic radiation. Therelaxation wavelength of the fluorescent reagent is also known. In theexample implementation, the patient is imaged with an endoscopic imagingsystem as discussed herein. The endoscopic imaging system pulsespartitions of red, green, and blue wavelengths of light to generate anRGB video stream of the interior of the patient's body. Additionally,the endoscopic imaging system pulses the excitation wavelength ofelectromagnetic radiation for the fluorescent reagent that wasadministered to the patient. In the example, the patient has cancerouscells and the fluorescent reagent has adhered to the cancerous cells.When the endoscopic imaging system pulses the excitation wavelength forthe fluorescent reagent, the fluorescent reagent will fluoresce and emita relaxation wavelength. If the cancerous cells are present in the scenebeing imaged by the endoscopic imaging system, then the fluorescentreagent will also be present in the scene and will emit its relaxationwavelength after fluorescing due to the emission of the excitationwavelength. The endoscopic imaging system senses the relaxationwavelength of the fluorescent reagent and thereby senses the presence ofthe fluorescent reagent in the scene. Because the fluorescent reagent isknown to adhere to cancerous cells, the presence of the fluorescentreagent further indicates the presence of cancerous cells within thescene. The endoscopic imaging system thereby identifies the location ofcancerous cells within the scene. The endoscopic imaging system mayfurther emit a laser scanning pulsing scheme for generating a topologyof the scene and calculating dimensions for objects within the scene.The location of the cancerous cells (as identified by the fluorescenceimaging data) may be combined with the topology and dimensionsinformation calculated based on the laser scanning data. Therefore, theprecise location, size, dimensions, and topology of the cancerous cellsmay be identified. This information may be provided to a medicalpractitioner to aid in excising the cancerous cells. Additionally, thisinformation may be provided to a robotic surgical system to enable thesurgical system to excise the cancerous cells.

In a further example implementation, a patient is imaged with anendoscopic imaging system to identify quantitative diagnosticinformation about the patient's tissue pathology. In the example, thepatient is suspected or known to suffer from a disease that can betracked with hyperspectral imaging to observe the progression of thedisease in the patient's tissue. The endoscopic imaging system pulsespartitions of red, green, and blue wavelengths of light to generate anRGB video stream of the interior of the patient's body. Additionally,the endoscopic imaging system pulses one or more hyperspectralwavelengths of light that permit the system to “see through” sometissues and generate imaging of the tissue that is affected by thedisease. The endoscopic imaging system senses the reflectedhyperspectral electromagnetic radiation to generate hyperspectralimaging data of the diseased tissue, and thereby identifies the locationof the diseased tissue within the patient's body. The endoscopic imagingsystem may further emit a laser scanning pulsing scheme for generating atopology of the scene and calculating dimensions of objects within thescene. The location of the diseased tissue (as identified by thehyperspectral imaging data) may be combined with the topology anddimensions information that is calculated with the laser scanning data.Therefore, the precise location, size, dimensions, and topology of thediseased tissue can be identified. This information may be provided to amedical practitioner to aid in excising, imaging, or studying thediseased tissue. Additionally, this information may be provided to arobotic surgical system to enable the surgical system to excise thediseased tissue.

FIG. 22 is a schematic diagram of an imaging system 2200 having a singlecut filter. The system 2200 includes an endoscope 2206 or other suitableimaging device having a light source 2208 for use in a light deficientenvironment. The endoscope 2206 includes an image sensor 2204 and afilter 2202 for filtering out unwanted wavelengths of light or otherelectromagnetic radiation before reaching the image sensor 2204. Thelight source 2208 transmits light that may illuminate the surface 2212in a light deficient environment such as a body cavity. The light 2210is reflected off the surface 2212 and passes through the filter 2202before hitting the image sensor 2204.

The filter 2202 may be used in an implementation where a fluorescentreagent or dye has been administered. In such an embodiment, the lightsource 2208 emits the excitation wavelength for fluorescing thefluorescent reagent or dye. Commonly, the relaxation wavelength emittedby the fluorescent reagent or dye will be of a different wavelength thanthe excitation wavelength. The filter 2202 may be selected to filter outthe excitation wavelength and permit only the relaxation wavelength topass through the filter and be sensed by the image sensor 2204.

In one embodiment, the filter 2202 is configured to filter out anexcitation wavelength of electromagnetic radiation that causes a reagentor dye to fluoresce such that only the expected relaxation wavelength ofthe fluoresced reagent or dye is permitted to pass through the filter2202 and reach the image sensor 2204. In an embodiment, the filter 2202filters out at least a fluorescent reagent excitation wavelength between770 nm and 790 nm. In an embodiment, the filter 2202 filters out atleast a fluorescent reagent excitation wavelength between 795 nm and 815nm. In an embodiment, the filter 2202 filters out at least a fluorescentreagent excitation wavelength between 770 nm and 790 nm and between 795nm and 815 nm. In these embodiments, the filter 2202 filters out theexcitation wavelength of the reagent and permits only the relaxationwavelength of the fluoresced reagent to be read by the image sensor2204. The image sensor 2204 may be a wavelength-agnostic image sensorand the filter 2202 may be configured to permit the image sensor 2204 toonly receive the relaxation wavelength of the fluoresced reagent and notreceive the emitted excitation wavelength for the reagent. The datadetermined by the image sensor 2204 may then indicate a presence of acritical body structure, tissue, biological process, or chemical processas determined by a location of the reagent or dye.

The filter 2202 may further be used in an implementation where afluorescent reagent or dye has not been administered. The filter 2202may be selected to permit wavelengths corresponding to a desiredspectral response to pass through and be read by the image sensor 2204.The image sensor 2204 may be a monochromatic image sensor such thatpixels of the captured image that exceed a threshold or fall below athreshold may be characterized as corresponding to a certain spectralresponse or fluorescence emission. The spectral response or fluorescenceemission, as determined by the pixels captured by the image sensor 2204,may indicate the presence of a certain body tissue or structure, acertain condition, a certain chemical process, and so forth.

FIG. 23 is a schematic diagram of an imaging system 2300 having multiplecut filters. The system 2300 includes an endoscope 2306 or othersuitable imaging device having a light source 2308 for use in a lightdeficient environment. The endoscope 2306 includes an image sensor 2304and two filters 2302 a, 2302 b. It should be appreciated that inalternative embodiments, the system 2300 may include any number offilters, and the number of filters and the type of filters may beselected for a certain purpose e.g., for gathering imaging informationof a particular body tissue, body condition, chemical process, and soforth. The filters 2302 a, 2302 b are configured for preventing unwantedwavelengths of light or other electromagnetic radiation from beingsensed by the image sensor 2304. The filters 2302 a, 2302 b may beconfigured to filter out unwanted wavelengths from white light or otherelectromagnetic radiation that may be emitted by the light source 2308.

Further to the disclosure with respect to FIG. 22 , the filters 2302 a,2302 b may be used in an implementation where a fluorescent reagent ordye has been administered. The filters 2302 a, 2302 b may be configuredfor blocking an emitted excitation wavelength for the reagent or dye andpermitting the image sensor 2304 to only read the relaxation wavelengthof the reagent or dye. Further, the filters 2302 a, 2302 b may be usedin an implementation where a fluorescent reagent or dye has not beenadministered. In such an implementation, the filters 2302 a, 2302 b maybe selected to permit wavelengths corresponding to a desired spectralresponse to pass through and be read by the image sensor 2304.

The multiple filters 2302 a, 2302 b may each be configured for filteringout a different range of wavelengths of the electromagnetic spectrum.For example, one filter may be configured for filtering out wavelengthslonger than a desired wavelength range and the additional filter may beconfigured for filtering out wavelengths shorter than the desiredwavelength range. The combination of the two or more filters may resultin only a certain wavelength or band of wavelengths being read by theimage sensor 2304.

In an embodiment, the filters 2302 a, 2302 b are customized such thatelectromagnetic radiation between 513 nm and 545 nm contacts the imagesensor 2304. In an embodiment, the filters 2302 a, 2302 b are customizedsuch that electromagnetic radiation between 565 nm and 585 nm contactsthe image sensor 2304. In an embodiment, the filters 2302 a, 2302 b arecustomized such that electromagnetic radiation between 900 nm and 1000nm contacts the image sensor 2304. In an embodiment, the filters 2302 a,2302 b are customized such that electromagnetic radiation between 425 nmand 475 nm contacts the image sensor 2304. In an embodiment, the filters2302 a, 2302 b are customized such that electromagnetic radiationbetween 520 nm and 545 nm contacts the image sensor 2304. In anembodiment, the filters 2302 a, 2302 b are customized such thatelectromagnetic radiation between 625 nm and 645 nm contacts the imagesensor 2304. In an embodiment, the filters 2302 a, 2302 b are customizedsuch that electromagnetic radiation between 760 nm and 795 nm contactsthe image sensor 2304. In an embodiment, the filters 2302 a, 2302 b arecustomized such that electromagnetic radiation between 795 nm and 815 nmcontacts the image sensor 2304. In an embodiment, the filters 2302 a,2302 b are customized such that electromagnetic radiation between 370 nmand 420 nm contacts the image sensor 2304. In an embodiment, the filters2302 a, 2302 b are customized such that electromagnetic radiationbetween 600 nm and 670 nm contacts the image sensor 2304. In anembodiment, the filters 2302 a, 2302 b are configured for permittingonly a certain fluorescence relaxation emission to pass through thefilters 2302 a, 2302 b and contact the image sensor 2304.

In an embodiment, the system 2300 includes multiple image sensors 2304and may particularly include two image sensors for use in generating athree-dimensional image. The image sensor(s) 2304 may becolor/wavelength agnostic and configured for reading any wavelength ofelectromagnetic radiation that is reflected off the surface 2312. In anembodiment, the image sensors 2304 are each color dependent orwavelength dependent and configured for reading electromagneticradiation of a particular wavelength that is reflected off the surface2312 and back to the image sensors 2304. Alternatively, the image sensor2304 may include a single image sensor with a plurality of differentpixel sensors configured for reading different wavelengths or colors oflight, such as a Bayer filter color filter array. Alternatively, theimage sensor 2304 may include one or more color agnostic image sensorsthat may be configured for reading different wavelengths ofelectromagnetic radiation according to a pulsing schedule such as thoseillustrated in FIGS. 5-7E, for example.

FIGS. 24A and 24B illustrate a perspective view and a side view,respectively, of an implementation of an imaging sensor 2400 having aplurality of pixel arrays for producing a three-dimensional image. Thethree-dimensional image sensor may be built on a plurality of substratesand may comprise the plurality of pixel arrays and other associatedcircuitry, wherein a plurality of pixel columns 2404 a forming the firstpixel array and a plurality of pixel columns 2404 b forming a secondpixel array are located on respective substrates 2402 a and 2402 b,respectively, and a plurality of circuit columns 2408 a and 2408 b arelocated on a separate substrate 2406. Also illustrated are theelectrical connections and communications between columns of pixels toassociated or corresponding column of circuitry.

The plurality of pixel arrays may sense information simultaneously andthe information from the plurality of pixel arrays may be combined togenerate a three-dimensional image. In an embodiment, an endoscopicimaging system includes two or more pixel arrays that can be deployed togenerate three-dimensional imaging. The endoscopic imaging system mayinclude an emitter for emitting pulses of electromagnetic radiationduring a blanking period of the pixel arrays. The pixel arrays may besynced such that the optical black pixels are read (i.e., the blankingperiod occurs) at the same time for the two or more pixel arrays. Theemitter may emit pulses of electromagnetic radiation for charging eachof the two or more pixel arrays. The two or more pixel arrays may readtheir respective charged pixels at the same time such that the readoutperiods for the two or more pixel arrays occur at the same time or atapproximately the same time. In an embodiment, the endoscopic imagingsystem includes multiple emitters that are each individual synced withone or more pixel arrays of a plurality of pixel arrays. Informationfrom a plurality of pixel arrays may be combined to generatethree-dimensional image frames and video streams.

FIGS. 25A and 25B illustrate a perspective view and a side view,respectively, of an implementation of a monolithic sensor 2500 having aplurality of pixel arrays for producing a three-dimensional image inaccordance with the teachings and principles of the disclosure. Such animplementation may be desirable for three-dimensional image capture,wherein the two-pixel arrays 2502 and 2504 may be offset during use. Inanother implementation, a first pixel array 2502 and a second pixelarray 2504 may be dedicated to receiving a predetermined range of wavelengths of electromagnetic radiation, wherein the first pixel array isdedicated to a different range of wavelength electromagnetic radiationthan the second pixel array.

FIGS. 26A and 26B illustrate a perspective view and a side view,respectively, of an implementation of an imaging sensor 2600 built on aplurality of substrates. As illustrated, a plurality of pixel columns2604 forming the pixel array are located on the first substrate 2602 anda plurality of circuit columns 2608 are located on a second substrate2606. Also illustrated in the figure are the electrical connection andcommunication between one column of pixels to its associated orcorresponding column of circuitry. In one implementation, an imagesensor, which might otherwise be manufactured with its pixel array andsupporting circuitry on a single, monolithic substrate/chip, may havethe pixel array separated from all or a majority of the supportingcircuitry. The disclosure may use at least two substrates/chips, whichwill be stacked together using three-dimensional stacking technology.The first 2602 of the two substrates/chips may be processed using animage CMOS process. The first substrate/chip 2602 may be comprisedeither of a pixel array exclusively or a pixel array surrounded bylimited circuitry. The second or subsequent substrate/chip 2606 may beprocessed using any process and does not have to be from an image CMOSprocess. The second substrate/chip 2606 may be, but is not limited to, ahighly dense digital process to integrate a variety and number offunctions in a very limited space or area on the substrate/chip, or amixed-mode or analog process to integrate for example precise analogfunctions, or a RF process to implement wireless capability, or MEMS(Micro-Electro-Mechanical Systems) to integrate MEMS devices. The imageCMOS substrate/chip 2602 may be stacked with the second or subsequentsubstrate/chip 2606 using any three-dimensional technique. The secondsubstrate/chip 2606 may support most, or a majority, of the circuitrythat would have otherwise been implemented in the first image CMOS chip2602 (if implemented on a monolithic substrate/chip) as peripheralcircuits and therefore have increased the overall system area whilekeeping the pixel array size constant and optimized to the fullestextent possible. The electrical connection between the twosubstrates/chips may be done through interconnects, which may be wirebonds, bump and/or TSV (Through Silicon Via).

It will be appreciated that the teachings and principles of thedisclosure may be used in a reusable device platform, a limited usedevice platform, a re-posable use device platform, or a singleuse/disposable device platform without departing from the scope of thedisclosure. It will be appreciated that in a re-usable device platforman end-user is responsible for cleaning and sterilization of the device.In a limited use device platform, the device can be used for somespecified amount of times before becoming inoperable. Typical new deviceis delivered sterile with additional uses requiring the end-user toclean and sterilize before additional uses. In a re-posable use deviceplatform, a third-party may reprocess the device (e.g., cleans, packagesand sterilizes) a single-use device for additional uses at a lower costthan a new unit. In a single use/disposable device platform a device isprovided sterile to the operating room and used only once before beingdisposed of.

EXAMPLES

The following examples pertain to preferred features of furtherembodiments:

-   -   Example 1 is a method. The method includes actuating an emitter        to emit a plurality of pulses of electromagnetic radiation and        sensing reflected electromagnetic radiation resulting from the        plurality of pulses of electromagnetic radiation with a pixel        array of an image sensor to generate a plurality of exposure        frames. The method includes generating a reference frame for use        in removing fixed pattern noise from the plurality of exposure        frames, wherein the reference frame is based on dark frame data        captured when the emitter is not emitting electromagnetic        radiation. The method includes reducing fixed pattern noise in        an exposure frame of the plurality of exposure frames by        subtracting the reference frame from the exposure frame. The        method is such that at least a portion of the plurality of        pulses of electromagnetic radiation emitted by the emitter        comprises electromagnetic radiation having a wavelength from        about 770 nm to about 790 nm.    -   Example 2 is a method as in Example 1, further comprising:        stopping the emitter from pulsing electromagnetic radiation; and        sensing the dark frame data with the pixel array when the        emitter is not emitting electromagnetic radiation.    -   Example 3 is a method as in any of Examples 1-2, wherein the        plurality of pulses of electromagnetic radiation are emitted in        a pattern of varying wavelengths of electromagnetic radiation,        and wherein the emitter repeats the pattern of varying        wavelengths of electromagnetic radiation.    -   Example 4 is a method as in any of Examples 1-3, wherein the        pattern of varying wavelengths of electromagnetic radiation        comprises a zero-emission period wherein the emitter does not        pulse electromagnetic radiation, and wherein the method further        comprises sensing the dark frame data with the pixel array        during the zero-emission period.    -   Example 5 is a method as in any of Examples 1-4, further        comprising sensing a plurality of dark exposure frames with the        pixel array when the emitter is not emitting electromagnetic        radiation, wherein each of the plurality of dark exposure frames        comprises dark frame data.    -   Example 6 is a method as in any of Examples 1-5, wherein the        plurality of dark exposure frames are interspersed within the        plurality of exposure frames.    -   Example 7 is a method as in any of Examples 1-6, wherein        generating the reference frame comprises generating a plurality        of reference frames based on the plurality of dark exposure        frames, and wherein the method further comprises enhancing        precision of at least one reference frame of the plurality of        reference frames by sampling subsequent dark frame data from        subsequent dark exposure frames.    -   Example 8 is a method as in any of Examples 1-7, wherein        enhancing precision of the at least one reference frame        comprises accounting for the subsequent dark frame data from the        subsequent dark exposure frames using exponential smoothing.    -   Example 9 is a method as in any of Examples 1-8, wherein        generating the reference frame comprises interpolating two or        more instances of dark frame data from two or more dark exposure        frames captured at different integration times.    -   Example 10 is a method as in any of Examples 1-9, wherein        sensing the reflected electromagnetic radiation comprises        sensing during a readout period of the pixel array, wherein the        readout period is a duration of time when active pixels in the        pixel array are read.    -   Example 11 is a method as in any of Examples 1-10, wherein        actuating the emitter comprises actuating the emitter to emit,        during a pulse duration, a plurality of sub-pulses of        electromagnetic radiation having a sub-duration shorter than the        pulse duration.    -   Example 12 is a method as in any of Examples 1-11, wherein        actuating the emitter comprises actuating the emitter to emit        two or more wavelengths simultaneously as a single pulse or a        single sub-pulse.    -   Example 13 is a method as in any of Examples 1-12, wherein        sensing the reflected electromagnetic radiation comprises        generating a fluorescence exposure frame, and wherein the method        further comprises providing the fluorescence exposure frame to a        corresponding system that determines a location of a critical        tissue structure within a scene based on the fluorescence        exposure frame.    -   Example 14 is a method as in any of Examples 1-13, further        comprising: receiving the location of the critical tissue        structure from the corresponding system; generating an overlay        frame comprising the location of the critical tissue structure;        and combining the overlay frame with a color image frame        depicting the scene to indicate the location of the critical        tissue structure within the scene.    -   Example 15 is a method as in any of Examples 1-14, wherein the        critical tissue structure comprises one or more of a nerve, a        ureter, a blood vessel, an artery, a blood flow, or a tumor.    -   Example 16 is a method as in any of Examples 1-15, further        comprising synchronizing timing of the plurality of pulses of        electromagnetic radiation to be emitted during a blanking period        of the image sensor, wherein the blanking period corresponds to        a time between a readout of a last row of active pixels in the        pixel array and a beginning of a next subsequent readout of        active pixels in the pixel array.    -   Example 17 is a method as in any of Examples 1-16, wherein        sensing the reflected electromagnetic radiation comprises        sensing with a first pixel array and a second pixel array such        that a three-dimensional image can be generated based on the        sensed reflected electromagnetic radiation.    -   Example 18 is a method as in any of Examples 1-17, wherein        actuating the emitter comprises actuating the emitter to emit a        sequence of pulses of electromagnetic radiation repeatedly        sufficient for generating a video stream comprising a plurality        of image frames, wherein each image frame in the video stream        comprises data from a plurality of exposure frames, and wherein        each of the exposure frames corresponds to a pulse of        electromagnetic radiation.    -   Example 19 is a method as in any of Examples 1-18, wherein at        least a portion of the plurality of pulses of electromagnetic        radiation emitted by the emitter is an excitation wavelength for        fluorescing a reagent, and wherein at least a portion of the        reflected electromagnetic radiation sensed by the pixel array is        a relaxation wavelength of the reagent.    -   Example 20 is a system. The system includes an emitter for        emitting a plurality of pulses of electromagnetic radiation and        an image sensor comprising a pixel array for sensing reflected        electromagnetic radiation to generate a plurality of exposure        frames. The system includes one or more processors configurable        to execute instructions stored in non-transitory computer        readable storage media. The instructions includes generating a        reference frame for use in removing fixed pattern noise from the        plurality of exposure frames, wherein the reference frame is        based on dark frame data. The instructions includes reducing        fixed pattern noise in an exposure frame of the plurality of        exposure frames by subtracting the reference frame from the        exposure frame. The system is such that at least a portion of        the pulses of electromagnetic radiation emitted by the emitter        comprises electromagnetic radiation having a wavelength from        about 770 nm to about 790 nm.    -   Example 21 is a system as in Example 20, wherein the        instructions further comprise: stopping the emitter from pulsing        electromagnetic radiation; and sensing the dark frame data with        the pixel array when the emitter is not emitting electromagnetic        radiation.    -   Example 22 is a system as in any of Examples 20-21, wherein the        plurality of pulses of electromagnetic radiation are emitted in        a pattern of varying wavelengths of electromagnetic radiation,        and wherein the emitter repeats the pattern of varying        wavelengths of electromagnetic radiation.    -   Example 23 is a system as in any of Examples 20-22, wherein the        pattern of varying wavelengths of electromagnetic radiation        comprises a zero-emission period wherein the emitter does not        pulse electromagnetic radiation, and wherein the method further        comprises sensing the dark frame data with the pixel array        during the zero-emission period.    -   Example 24 is a system as in any of Examples 20-23, wherein the        pixel array senses a plurality of dark exposure frames over a        plurality of instances when the emitter is not emitting        electromagnetic radiation, wherein each of the plurality of dark        exposure frames comprises dark frame data.    -   Example 25 is a system as in any of Examples 20-24, wherein the        instructions are such that generating the reference frame        comprises generating a plurality of reference frames based on        the plurality of dark exposure frames, and wherein the method        further comprises enhancing precision of at least one reference        frame of the plurality of reference frames by sampling        subsequent dark frame data from subsequent dark exposure frames.    -   Example 26 is a system as in any of Examples 20-25, wherein at        least a portion of the pulses of electromagnetic radiation        emitted by the emitter results in a fluorescence exposure frame        created by the image sensor, and wherein the instructions        further comprise providing the fluorescence exposure frame to a        corresponding system that determines a location of a critical        tissue structure within a scene based on the fluorescence        exposure frame.    -   Example 27 is a system as in any of Examples 20-26, wherein the        instructions further comprise: receiving the location of the        critical tissue structure from the corresponding system;        generating an overlay frame comprising the location of the        critical tissue structure; and combining the overlay frame with        a color image frame depicting the scene to indicate the location        of the critical tissue structure within the scene.    -   Example 28 is a system as in any of Examples 20-27, wherein the        critical tissue structure comprises one or more of a nerve, a        ureter, a blood vessel, an artery, a blood flow, or a tumor.    -   Example 29 is a system as in any of Examples 20-28, wherein the        image sensor comprises a first image sensor and a second image        sensor such that the image sensor can generate a        three-dimensional image.    -   Example 30 is a system as in any of Examples 20-29, further        comprising a filter that filters electromagnetic radiation        having a wavelength from about 770 nm to about 790 nm.    -   Example 31 is a system as in any of Examples 20-30, further        comprising a filter that filters electromagnetic radiation        having a wavelength from about 795 nm to about 815 nm.    -   Example 32 is a means for performing any of the methods depicted        in Examples 1-19.

It will be appreciated that various features disclosed herein providesignificant advantages and advancements in the art. The following claimsare exemplary of some of those features.

In the foregoing Detailed Description of the Disclosure, variousfeatures of the disclosure are grouped together in a single embodimentfor the purpose of streamlining the disclosure. This method ofdisclosure is not to be interpreted as reflecting an intention that theclaimed disclosure requires more features than are expressly recited ineach claim. Rather, inventive aspects lie in less than all features of asingle foregoing disclosed embodiment.

It is to be understood that any features of the above-describedarrangements, examples, and embodiments may be combined in a singleembodiment comprising a combination of features taken from any of thedisclosed arrangements, examples, and embodiments.

It is to be understood that the above-described arrangements are onlyillustrative of the application of the principles of the disclosure.Numerous modifications and alternative arrangements may be devised bythose skilled in the art without departing from the spirit and scope ofthe disclosure and the appended claims are intended to cover suchmodifications and arrangements.

Thus, while the disclosure has been shown in the drawings and describedabove with particularity and detail, it will be apparent to those ofordinary skill in the art that numerous modifications, including, butnot limited to, variations in size, materials, shape, form, function andmanner of operation, assembly and use may be made without departing fromthe principles and concepts set forth herein.

Further, where appropriate, functions described herein can be performedin one or more of: hardware, software, firmware, digital components, oranalog components. For example, one or more application specificintegrated circuits (ASICs) or field programmable gate arrays (FPGAs)can be programmed to carry out one or more of the systems and proceduresdescribed herein. Certain terms are used throughout the followingdescription and claims to refer to particular system components. As oneskilled in the art will appreciate, components may be referred to bydifferent names. This document does not intend to distinguish betweencomponents that differ in name, but not function.

The foregoing description has been presented for the purposes ofillustration and description. It is not intended to be exhaustive or tolimit the disclosure to the precise form disclosed. Many modificationsand variations are possible in light of the above teaching. Further, itshould be noted that any or all the aforementioned alternateimplementations may be used in any combination desired to formadditional hybrid implementations of the disclosure.

Further, although specific implementations of the disclosure have beendescribed and illustrated, the disclosure is not to be limited to thespecific forms or arrangements of parts so described and illustrated.The scope of the disclosure is to be defined by the claims appendedhereto, any future claims submitted here and in different applications,and their equivalents.

What is claimed is:
 1. A method comprising: actuating an emitter to emita plurality of pulses of electromagnetic radiation; sensing reflectedelectromagnetic radiation resulting from the plurality of pulses ofelectromagnetic radiation with a pixel array of an image sensor togenerate a plurality of exposure frames; generating a reference framefor use in removing fixed pattern noise from the plurality of exposureframes, wherein the reference frame is based on dark frame data capturedwhen the emitter is not emitting electromagnetic radiation; samplingdark frame data captured when the emitter is not emittingelectromagnetic radiation to generate a plurality of dark referenceframes; and storing pixel data for a recently captured dark referenceframe in a buffer; wherein at least a portion of the plurality of pulsesof electromagnetic radiation emitted by the emitter comprises afluorescence excitation wavelength for fluorescing a reagent; andwherein sensing the reflected electromagnetic radiation comprisesgenerating a fluorescence exposure frame in response to an emission ofthe fluorescence excitation wavelength.
 2. The method of claim 1,wherein the fluorescence excitation wavelength comprises electromagneticradiation having a wavelength from about 770 nm to about 795 nm.
 3. Themethod of claim 1, further comprising: stopping the emitter from pulsingelectromagnetic radiation; and sensing the dark frame data with thepixel array when the emitter is not emitting electromagnetic radiation.4. The method of claim 1, wherein: the plurality of pulses ofelectromagnetic radiation are emitted in a pattern of varyingwavelengths of electromagnetic radiation comprising a zero-emissionperiod wherein the emitter does not pulse electromagnetic radiation; theemitter repeats the pattern of varying wavelengths of electromagneticradiation; and the method further comprises sensing the dark frame datawith the pixel array during the zero-emission period.
 5. The method ofclaim 1, further comprising sensing a plurality of dark exposure frameswith the pixel array when the emitter is not emitting electromagneticradiation, wherein each of the plurality of dark exposure framescomprises dark frame data, and wherein the plurality of dark exposureframes are interspersed within the plurality of exposure frames.
 6. Themethod of claim 5, wherein generating the reference frame comprisesgenerating a plurality of reference frames based on the plurality ofdark exposure frames, and wherein the method further comprises enhancingprecision of at least one reference frame of the plurality of referenceframes by sampling subsequent dark frame data from subsequent darkexposure frames.
 7. The method of claim 6, wherein enhancing theprecision of the at least one reference frame comprises accounting forthe subsequent dark frame data from the subsequent dark exposure framesusing exponential smoothing.
 8. The method of claim 1, whereingenerating the reference frame comprises interpolating two or moreinstances of dark frame data from two or more dark exposure framescaptured at different integration times.
 9. The method of claim 1,further comprising: enhancing precision of the reference frame by:updating the pixel data stored in the buffer with a first correctionfactor; modifying pixel data for a newly captured dark reference framewith a second correction factor; and combining the modified pixel datastored in the buffer with the modified pixel data for the newly captureddark reference frame.
 10. The method of claim 1, wherein sensing thereflected electromagnetic radiation comprises sensing during a readoutperiod of the pixel array, wherein the readout period is a duration oftime when active pixels in the pixel array are read.
 11. The method ofclaim 1, wherein actuating the emitter comprises actuating the emitterto emit, during a pulse duration, a plurality of sub-pulses ofelectromagnetic radiation having a sub-duration shorter than the pulseduration.
 12. The method of claim 1, wherein actuating the emittercomprises actuating the emitter to emit two or more wavelengthssimultaneously as a single pulse or a single sub-pulse.
 13. The methodof claim 1, wherein the method further comprises providing thefluorescence exposure frame to a corresponding system that determines alocation of a tissue structure within a scene based on the fluorescenceexposure frame.
 14. The method of claim 13, further comprising:receiving the location of the tissue structure from the correspondingsystem; generating an overlay frame comprising the location of thetissue structure; and combining the overlay frame with a color imageframe depicting the scene to indicate the location of the tissuestructure within the scene.
 15. The method of claim 14, wherein thetissue structure comprises one or more of a nerve, a ureter, a bloodvessel, an artery, a blood flow, or a tumor.
 16. The method of claim 1,further comprising synchronizing timing of the plurality of pulses ofelectromagnetic radiation to be emitted during a blanking period of theimage sensor, wherein the blanking period corresponds to a time betweena readout of a last row of active pixels in the pixel array and abeginning of a next subsequent readout of active pixels in the pixelarray.
 17. The method of claim 1, wherein actuating the emittercomprises actuating the emitter to emit a sequence of pulses ofelectromagnetic radiation repeatedly sufficient for generating a videostream comprising a plurality of image frames, wherein each image framein the video stream comprises data from a plurality of exposure frames,and wherein each of the plurality of exposure frames corresponds to apulse of electromagnetic radiation.
 18. The method of claim 1, whereinat least a portion of the reflected electromagnetic radiation sensed bythe pixel array is a relaxation wavelength of the reagent in response tothe emitter pulsing the fluorescence excitation wavelength.
 19. A systemcomprising: an emitter for emitting a plurality of pulses ofelectromagnetic radiation; an image sensor comprising a pixel array forsensing reflected electromagnetic radiation to generate a plurality ofexposure frames; and one or more processors configurable to executeinstructions stored in non-transitory computer readable storage media,the instructions comprising: generating a reference frame for use inremoving fixed pattern noise from the plurality of exposure frames,wherein the reference frame is based on dark frame data captured whenthe emitter is not emitting electromagnetic radiation; and reducingfixed pattern noise in an exposure frame of the plurality of exposureframes by subtracting the reference frame from the exposure frame;wherein at least a portion of the pulses of electromagnetic radiationemitted by the emitter comprises a fluorescence excitation wavelengthfor fluorescing a reagent.
 20. The system of claim 19, wherein thefluorescence excitation wavelength comprises electromagnetic radiationhaving a wavelength from about 770 nm to about 795 nm.
 21. The system ofclaim 19, wherein the instructions further comprise: stopping theemitter from pulsing electromagnetic radiation; and sensing the darkframe data with the pixel array when the emitter is not emittingelectromagnetic radiation.
 22. The system of claim 19, wherein: theplurality of pulses of electromagnetic radiation emitted by the emitterare emitted in a pattern of varying wavelengths of electromagneticradiation comprising a zero-emission period wherein the emitter does notpulse electromagnetic radiation; the emitter repeats the pattern ofvarying wavelengths of electromagnetic radiation; and the pixel arraysenses the dark frame data during the zero-emission period.
 23. Thesystem of claim 19, wherein the pixel array senses a plurality of darkexposure frames over a plurality of instances when the emitter is notemitting electromagnetic radiation, wherein each of the plurality ofdark exposure frames comprises dark frame data.
 24. The system of claim23, wherein the instructions are such that generating the referenceframe comprises generating a plurality of reference frames based on theplurality of dark exposure frames, and wherein the method furthercomprises enhancing precision of at least one reference frame of theplurality of reference frames by sampling subsequent dark frame datafrom subsequent dark exposure frames.
 25. The system of claim 19,wherein at least a portion of the pulses of electromagnetic radiationemitted by the emitter results in a fluorescence exposure frame createdby the image sensor, and wherein the instructions further compriseproviding the fluorescence exposure frame to a corresponding system thatdetermines a location of a tissue structure within a scene based on thefluorescence exposure frame.
 26. The system of claim 25, wherein theinstructions further comprise: receiving the location of the tissuestructure from the corresponding system; generating an overlay framecomprising the location of the tissue structure; and combining theoverlay frame with a color image frame depicting the scene to indicatethe location of the tissue structure within the scene.
 27. The system ofclaim 26, wherein the tissue structure comprises one or more of a nerve,a ureter, a blood vessel, an artery, a blood flow, or a tumor.
 28. Thesystem of claim 19, wherein the image sensor comprises a first imagesensor and a second image sensor such that the image sensor can generatea three-dimensional image.
 29. The system of claim 19, furthercomprising a filter that filters electromagnetic radiation having awavelength from about 770 nm to about 795 nm.